Hepatitis B Virus (HBV) is a challenge for global health services, affecting millions and leading hundreds to end-stage liver disease each year. This comprehensive review explores the interactions between HBV and the host, examining their impact on clinical outcomes. HBV infection encompasses a spectrum of severity, ranging from acute hepatitis B to chronic hepatitis B, which can potentially progress to cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B infection (OBI), characterized by low HBV DNA levels in hepatitis B surface antigen-negative individuals, can reactivate and cause acute hepatitis B. The identification of diverse HBV genotypes reveals distinct geographical distributions and associations with clinical outcomes. Moreover, single nucleotide polymorphisms (SNPs) within the host genome have been linked to several clinical outcomes, including cirrhosis, HCC, OBI, hepatitis B reactivation, and spontaneous clearance. The immune response plays a key role in controlling HBV infection by eliminating infected cells and neutralizing HBV in the bloodstream. Furthermore, HBV can modulate host metabolic pathways involved in glucose and lipid metabolism and bile acid absorption, further influencing disease progression. HBV clinical outcomes correlate with three levels of viral adaptation. In conclusion, the clinical outcomes of HBV infection could result from complex immune and metabolic interactions between the host and HBV. These outcomes can vary among populations and are influenced by HBV genotypes, host genetics, environmental factors, and lifestyle. Understanding the degrees of HBV adaptation is essential for developing region-specific control and prevention measures.

Being a great source of protein, B-vitamins and minerals, meat and fish are staple foods in many cultures. However, cooking at high temperatures can produce chemicals associated with an increased risk of developing cancer. This review investigates the possible carcinogenic activity of chemicals formed during the cooking of meat and fish including heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), and advanced glycation end products (AGEs). High-temperature cooking methods for meat, including grilling or frying, result in the formation of HCAs. Meat that has been smoked, grilled, or cooked over an open flame produces PAHs whereas, dry heat methods including roasting, grilling, and frying results in formation of AGEs. In vitro studies have shown that these compounds can damage DNA, cause mutations, and promote the growth of cancer cells. Research shows that thoroughly cooked meat increases the risk of cancer, particularly colorectal, pancreatic, and prostate cancer. Alternative cooking techniques, marinades, and incorporating fruits and vegetables can help to mitigate this risk. For determining the efficacy of these measures, additional studies are required. For the purpose of lowering the potential carcinogenic activity of chemicals formed during the cooking of meat and fish, mitigation techniques must be understood and put into practice. Cancer can be avoided by informing people about the dangers of eating meat and fish that have been cooked at high temperatures and by encouraging better diets and cooking styles. In order to lessen the possible health concerns related to the eating of meat and fish, further studies are required.

Predicting the outcome of a future game between two National Basketball Association (NBA) teams poses a challenging problem of interest to statistical scientists as well as the general public. In this article, we formalize the problem of predicting the game results as a classification problem and apply the principle of maximum entropy to construct NBA maximum entropy (NBAME) model that fits to discrete statistics for NBA games, and then predict the outcomes of NBA playoffs by the NBAME model. The best NBAME model is able to correctly predict the winning team 74.4 percent of the time as compared to some other machine learning algorithms which is correct 69.3 percent of the time.

The development of plant-based meat analogues has become a significant challenge for the food industry in recent years due to the increasing demand for sustainable and healthier proteins in the context of a global protein transition. Plant-based meat analogues imitate the visual, textural, and chemical properties of traditional meat products and are required to closely resemble meat to appeal to consumers. In addition, consumers demand natural, clean-label, and nutritional and healthy products. To address these challenges, the food industry must develop highly healthy, nutritious, and E-number-free meat analogue products. Understanding the functionality of each ingredient and its role in the food matrix is crucial to being a key player in the innovation of the meat analogues market. This review provides updated information on the primary ingredients utilized for the development of plant-based burger meat alternatives and their functionality. The key components of meat analogue burgers are outlined, including plant proteins, binding agents, fats and oils, flavorings, colorings, preservatives, fortificants, and clean-label considerations.

DIEP-based breast reconstruction necessitates wide undermining at the abdominal donor-site, creating large wound areas. Flap harvesting is usually conducted using electrosurgical dissection devices. This study sought to compare the clinical outcomes in patients after using the PEAK PlasmaBlade (PPB) versus monopolar electrocautery (MPE). This retrospective cohort study included 128 patients with DIEP-based breast reconstruction. Patient characteristics as well as information on the postoperative course were collected and a comparative evaluation was conducted. The MPE group exhibited significantly (p* = 0.0324) higher abdominal drainage volume (351.11 ± 185.96 ml) compared to the PPB group (279.38 ± 183.38 ml). Subgroup analysis demonstrated that PPB significantly reduced postoperative wound fluid in patients with BMI > 30 kg/m² (p* = 0.0284), without prior neoadjuvant chemotherapy (p** = 0.0041), and among non-smokers (p = 0.0046). Furthermore, postoperative pain was significantly (p**** < 0.0001) lower in the PPB cohort. This study confirms the non-inferiority of the PEAK PlasmaBlade to conventional electrocautery for abdominal flap harvesting. The PPB demonstrated advantages, notably reduced drainage volume and lower postoperative pain levels. Recognizing patient subsets that benefit more from the PPB highlights the importance of personalized device selection based on patient characteristics.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

Urea cycle disorders (UCDs) are common inborn errors of metabolism, with an incidence of one in 30,000 births. They are caused by deficiencies in any of six enzymes and two carrier proteins, the most common being Ornithine Transcarbamylase Deficiency (OTCD). OTCD results in impairment to excrete nitrogen, causing toxic buildup of ammonia with resultant encephalopathy. Hyperammonemia (HA) induces the conversion of glutamate to glutamine in the brain. Excess glutamine in the brain causes osmotic changes cerebral edema, changes in astrocyte morphology, and cell death. Acute symptoms of HA include vomiting, hyperventilation, seizures, and irritability. Long-term neurological changes include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of plasma ammonia level at presentation and duration of hyperammonemic coma. We provide a comprehensive analysis of a 16-year-old male with neonatal onset of OTCD as an example of how brain biomarkers may be useful to monitor disease course and outcome. This male presented at 8 days post natal with plasma ammonia and glutamine of 677 and 4024 micromol/L and had a missense mutation in Exon 4 (p.R129H). Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. He suffered recurrent acute hyperammonemic episodes despite compliance, triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI based disease biomarkers.

Introduction: Hospitalization in a COVID-19 unit represents a significant source of stress and psychological distress for patients. Our study aims to determine the factors of psychological distress in the therapeutic and psychosocial management of patients hospitalized with a COVID-19 infection. Methods: This cross-sectional study was carried out over 8 months at the COVID-19 zone of the CHU HASSAN II of FES. 99 patients were evaluated within days of diagnosis by psychometric scales of anxiety, depression, and post-traumatic stress. In the course of this follow-up, we found the presence of psychological impacts in these patients, and we tried to find correlating factors between the occurrence of psychiatric disorders and the set of factors related to sociodemographic data, hospitalization course and treatments taken, as well as family support. Results: 35% of patients had scores in favor of post-traumatic stress disorder, 37% of the patients had definite depression and 50% had anxiety. Post-traumatic stress, depression, and anxiety were correlated with sociodemographic factors, hospitalization, treatments received, and length of stay. Conclusion: The prevalence of anxiety-depressive disorders and post-traumatic stress disorder was high in patients with COVID-19, hence the interest in providing psychological and psychosocial care in the emergency department.

Mannosylerythritol lipids (MELs), one of the most promising biosurfactants (BS), are glycolipids produced by yeasts or fungi, with great environmental performance and a high compatibility with the human body. MELs besides working as typical surfactants, can form diverse structures when in the critical aggregation concentration (CAC), reducing the surface tension of water and other solutions, and being stable over a wide range of conditions. Among others, MELs present anti-microbial, antitumor, antioxidant and anti-inflammatory activity, skin and hair repair capacity, which opens possibilities for their use in applications from cosmetics and pharmaceutics to bio-remediation and agriculture. However, their market share is still low when compared to other glycolipids, due to their less developed production process and higher production cost. This re-view gathers information on the potential applications of MELs mentioned on the literature since 1993. Furthermore, it is also explored the current strategies being developed to enhance the market presence of MELs, in parallel with the ones developed for rhamnolipids and sophorolipids.

The growing demand for nutritious foods has spurred investigations into alternative sources of nutrition beyond traditional options. For this reason, the present study approaches the amaranth, which is a plant with high potential, highlighting the morphological growth, grain biomass pro-duction, and quantitative traits of seven varieties of amaranth cultivated in the pedoclimatic con-ditions of Somes meadow in Transylvania. A bifactorial trial was implemented with factors ama-ranth species and amaranth varieties. Two amaranth species and seven varieties were studied. Differences are reported between morpho-productive and quantitative traits of the seven amaranth varieties studied in this research. The interrelationships between amaranth morphological traits quantified by using Pearson simple correlations show that morphological traits moderately con-tribute to grain fresh biomass yield, while morphological traits and fresh biomass strongly con-tributed to grains dry biomass yield. Our study shows that morpho-productive, and nutritional characteristics of the seven amaranth varieties comprised by our study recommend the plans to be used in various nutritional aims, being a valuable replacer of traditional raw materials in specific food and feed industry sectors.

The bioactive marine sulfated polysaccharides ulvan and carrageenan, formulated in gels at 1.5, 5.0 and 10% w/w concentrations, were evaluated for their wound healing potential on second-degree burn wounds. The polysaccharide-based gels were administered on the burn-inflamed skin of hairless female SKH-hr2 mice, and the therapeutic effect of the various treatments was assessed based on histopathological analysis, the clinical condition of mice, photo-documentation, evaluation of biophysical skin parameters, and FT-IR spectroscopy.Clinical and histopathological assessment, as well as the reduction rate of the burn wound area, indicated that the 10% w/w carrageenan gel significantly enhanced wound healing, especially at the early stages of the healing process, recovering both the α-helix of collagen and the glycosaminoglycans configuration as evidenced by the FT-IR absorption bandsof skin in vivo and ex vivo. At later stages, the healing effect of the 5% w/w ulvan gel was also notably significant, indicating that carrageenan and ulvan wound dressing gels could potentially contribute to the efficient wound healing of burn wounds.

Proposed fundamental laws of biology and a model of health and disease underscore the importance of the lymphatic system. The lymphatics are responsible for two of the laws of biology and the fulcrum of health and disease balancing proliferation with regeneration through the immune system. It is responsible for protection from the environment and repair of senile and damaged tissue. Life is constantly bombarded by forces that increase entropy. Lymphatics provide negative entropy to maintain health. Lymphatics help maintain cellular homeostasis removing products of metabolism. Using these principles, the role of lymphatics is investigated in salt sensitivity hypertension, cardiorenal system, the new pillar of heart failure and kidney disease - Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors, and brain diseases. The realization of organ lymphatics in maintenance of health and disease opens the avenue to new therapeutics. This is the unrealized potential of lymphatic study.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

Severe malaria is a major public health concern in Angola, particularly among adults, with limited data on clinical outcomes and manifestations. The study therefore assessed the clinical manifestations and outcome of severe Plasmodium falciparum malaria in adult patients admitted to Hospital Central Dr. António Agostinho Neto of Lubango, Angola. The study retrospectively reviewed the individual records of patients over 14 years old, admitted for severe malaria during the first trimester of 2021 and 2022. World Health Organization (WHO) criteria were used to define severity. A total of 640 patients were recorded into the study, 167 in 2021 and 473 in 2022, distributed across the departments; Intensive Care Unit (ICU; n=81), Medicine (MED; n=458) and Infectiology (INF; n=101). The median age was 26 years and 59.4% were males. The most common manifestation of severe malaria was renal impairment (37.4%). The overall mortality rate was 7% and decreased considerably from 10.2% in 2021 to 5.9% in 2022. The increase in malaria cases during 2022 with increased in prevalence of life-threatening signs like renal impairment, jaundice and impaired conscience, underscores the urgent need for enhanced malaria control and surveillance strategies to mitigate morbidity and mortality, highlighting the potential for antimalarial drug resistance.

Introduction: An increasing body of evidence shows the significant role of the angiogenic factor levels in screening of pregnancy outcome. Purpose: To examine the potential relationship between concentrations of placental protein 13 (PP13) and soluble Human Leukocyte Antigen-G (sHLA-G) in maternal serum and amniotic fluid at 16-23 weeks of gestation and the sonographic features of pregnancy as well as pregnancy outcome. Materials and methods: PP13 and sHLA-G in serum and amniotic fluid, and fetal biometrical data and placental volume and perfusion indices were determined in 71 euploid, singleton pregnancies. Results: The serum sHLA-G level correlated negatively with serum PP13 level (r = -0.186, p&lt;0.001) and positively with sHLA-G level in the amniotic fluid (r = 0.662, p&lt;0.001). Significant correlation was found between serum sHLA-G level and placental volume (r = 0.142, p&lt;0.05) and between amniotic sHLA-G level and placental perfusion (r = -0.450, p&lt;0.001). A low amniotic PP13 level significantly predicted the birth weight (r = -0.102, p&lt;0.05), the duration of pregnancy (r = -0.155, p&lt;0.05), and the fetal abdominal circumference (r=-0.098, p&lt;0.05). Conclusions: PP13 assayed in amniotic fluid might be a potential marker of fetal growth and sHLA-G can be an adjunct modality reflecting placental sonographic parameters.

German noise action plans aim to reduce negative health outcomes from noise exposure and identify quiet areas free of noise pollution. Quiet area identification in German noise action plans is based primarily on noise mapping and spatial analysis and not empirical or qualitative data about acoustic environments, thus leaving a gap in the understanding of the quality of formally recognized quiet areas in noise action plans. This work presents a comparative empirical case study in Dortmund, Germany, with the aim to describe the diurnal dB(A) and biophonic properties of quiet areas versus noise 'hot spots'. Sound observations were collected (n=282,764) in five different natural or recreational land use patch types larger than four acres within 33 proposed quiet areas in Dortmund (n=70) and 23 noise hot spots between April 27^th, 2022 and March 2^nd, 2023. We find that quiet areas are on average more than 20 dB(A) quieter than noise hot spots almost every hour of the day. Forests, managed tree stands, cemeteries, and agriculture diel patterns are dominated by dawn dusk chorus in spring and summer, whereas sport and recreation as well as noise hot spots are dominated by traffic and human noise. A novel composite biophony mapping procedure is presented that finds distinct temporal distribution of biophony in forested and agriculture peri-urban locations positively associated with patch size, distance away from LDEN > 55, proximity to water, and the number of vegetation layers in the plant community. Anthrophony distribution dominates urban land uses in all hours of the day, but expands during day and evening and contracts at night and in dusk hours. The procedures presented here illustrate how qualitative information regarding quiet areas can be integrated into German noise action planning.

High hopes were associated with the new anti-angiogenic medicament, bevacizumab, which due to the possibility of binding to isoform A of vascular endothelial growth factor (VEGF), inhibited the creation of new blood vessels. However, not only blood vessels are responsible for the tumor cells' spread. During the process of tumor growth, lymphangiogenesis is mediated by other isoforms of the VEGF family, specifically VEGF-C and VEGF-D, which are independent of the bevacizumab action. Therefore, based on the mechanism of bevacizumab action and the processes of angio- and lymphangiogenesis, we formed three hypotheses: 1) if the lymph nodes in the primary ovarian cancers are metastatic, the outcome of bevacizumab treatment is worsened; 2) concerning the second-line treatment, bevacizumab will act in a weakened manner if the recurrence occurs in lymph nodes compared to local recurrences; 3) patients treated by bevacizumab are more likely to have recurrences in lymph nodes. These hypotheses raise the issue of the existing gap of knowledge, which concerns the effect of bevacizumab on the metastatic lymph nodes.

Cancer treatment is a significant focus in medicine owing to the increasing global incidence. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with the supplementation of natural products may confer benefits to cancer patients by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.

This study introduces and demonstrates a comprehensive, accurate, unbiased approach to robust quantitative comparison of Electronic Nicotine Delivery Systems (ENDS) appropriate for establishing substantial equivalence (or lack thereof) between tobacco products. The approach is demonstrated across a family of thirteen pen- and pod-style ENDS products. Methods employed consist of formulating a robust emissions surface regression model, quantifying the empirical accuracy of the model as applied to each product, evaluating relationships between product design characteristics and maximum emissions characteristics, and presenting results in formats useful to researchers, regulators, and consumers. Results provide a response surface to characterize emissions (total particulate matter and constituents thereof) from each ENDS appropriate for use in a computer model and for conducting quantitative exposure comparisons between products. Results demonstrate that emissions vary as a function of puff duration, flow rate, E-Liquid composition, and device operating power. Further, results indicate that regulating design characteristics of ENDS devices and consumables may not achieve desired public health outcomes; it is more effective to regulate maximum permissible emissions directly. Three emissions outcome measures (yield per puff, mass concentration and constituent mass ratio) are recommended for adoption as standard quantities for reporting by manufacturers and research laboratories. The approach provides a means of (a) quantifying and comparing maximal emissions from ENDS products spanning their entire operating envelope, (b) comparative evaluation of ENDS devices and consumable design characteristics, and (c) establishing comparative equivalence of maximal emissions from ENDS. A consumer-oriented product emissions dashboard is proposed for comparative evaluation of ENDS exposure potential. Maximum achievable power dissipated in the coil of ENDS is identified as a potentially effective regulatory parameter.

Spodoptera frugiperda (J.E. Smith) is a global agricultural pest that poses a threat to crop production, characterized by its refractory polyphagous nature that makes it difficult to control and may lead to damage to woody plants. However, research on its adaptability to woody plants remains limited. This study compares the feeding adaptations (survival rate, pupation time, pupation rate, weight, length, and feeding volume), protective enzyme activities, and feeding preferences of S. frugiperda on leaves of six economically significant tree species (Areca catechu, Aquilaria sinensis, Cocos nucifera, Camellia oleifera, Dalbergia odorifera and Hevea brasiliensis) and maize as a control treatment. The results indicate that A. sinensis as the most vulnerable trees in high risk, H. brasiliensis and C. nucifera presented varying degrees of susceptibility, A. catechu, C. oleifera, and D. odorifera were unsuitability for S. frugiperda. In conclusion, this report extensively explores the feeding effects of S. frugiperda on six economically important tree species, and provides insights into the feeding preferences on these plants, thereby informing the potential threat posed by S. frugiperda to economically vital trees.

Keywords: retinoblastoma, RB, gastric inhibitory polypeptide receptor, GIPR, trefoil factor family peptide, TFF1, CAM, tumorigenesis, MK0893, miR5-542-5p

Background Homologous recombination deficiency (HRD) evolved into a major diagnostic marker in high grade ovarian cancer (HGOC) predicting the response to poly (Adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences treatment response and patient survival; miliary type tumor spread has poorer predicted outcome than non-miliary type tumor spread. Methods Known methods for HRD assessment were adapted for our technical requirements and the Predictive-value Integrated Genomic Instability Score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results We demonstrated that PIGIS can discriminate HRD positive from HRD negative samples. Tumors with miliary tumor spread are HRD negative and have a very bad prognosis with a progression free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years), similar to HRD positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions Our results indicate that in a predominantly PARPi naïve cohort the type of tumor spread might be a better predictor of response to platinum sensitivity than HRD. It remains to be determined, whether this also applies for sensitivity to PARPi.

Reducing GHG emissions is a crucial challenge in urban areas, characterized by high energy consumption and reduced exposure to nature. In this context, the urban green system could play a pivotal role. In the literature, scholars analyzed both the ability of species-specific and layout-specific green infrastructures to increase carbon sequestration and the best location sites of new green infrastructures, to increase the provision of overall ecosystem services. There is a lack of studies helping green urban planners and designers choose where and which green infrastructure to implement, based on vegetation species-specific performance and local carbon emissions of city components. This paper uses tree inventory data from a medium-sized city in central Italy (Perugia) to develop a spatial analysis of the urban parks' performance in carbon sequestration. Then, the method evaluates the carbon emission of a public city building to generate a spatialized balance between buildings’ demand and trees’ supply, to support local decisions about the best locations for new green infrastructures and the choice between species. The paper contributes to GIS-based tools that vary the recommended location sites and species for new green infrastructures based on the demanded ecosystem service.

Cell-culture meat is a novel concept to replace traditional meat produced from animals, and to satisfy rising food demands due to the world population growth. It is still a young field and requires to solve technical issues including cell sources and types, efficient culture for large scale production, taste and texture for customer satisfaction. The current review summarized traditional beef meat production and evaluation methods for customer satisfaction. In particular, serum biomarkers for beef meat evaluation are discussed, which can be applicated for cell-culture meat production.

Intracranial metastases from thyroid cancer are rare. Although the prognosis of thyroid cancer patients is generally favorable, the prognosis of patients with intracranial metastases from thyroid cancer has been considered unfavorable having a lower survival rate than those without intracranial involvement. Many questions about their management remain unclear. The aim of this study was to analyze the characteristics, treatments, and outcomes of patients with brain metastases from thyroid cancer. Among 4320 patients with thyroid cancer recorded in our institutional database over a 30-year period, 20 patients with brain metastasis were retrospectively collected and analyzed. The clinical characteristics, histological type of primary cancer and metastatic brain tumor, additional previous distant metastasis, treatment modalities, locations and characteristics on radiologic findings, time interval between the first diagnosis of the primary thyroid cancer and brain metastasis, and survival were analyzed. The mean age at initial diagnosis was 59.3 ± 14.1 years, and at the manifestation of diagnosis of cerebral metastasis 64.8 ± 14.9 years. The histological types of the primary thyroid cancers were papillary in ten patients, follicular in seven, and poorly differentiated carcinoma in three. The average interval between the diagnosis of thyroid cancer and brain metastasis was 63.4 ± 58.4 months (range, 0-180 months). Ten patients had a single intracranial lesion and 10 patients had multiple lesions. Surgical resection was primarily performed in 15 patients and whole-brain radiotherapy, radiotherapy or tyrosine kinase inhibitors were applied in the other 5 patients. Overall median survival time was 15 months after diagnosis of BM from TC (range: 1-252 months). Patients with thyroid cancer can develop brain metastasis even many years after diagnosis of the primary tumor. Our study demonstrates an increased overall survival of patients younger than 60 years of age at the time of diagnosis of brain metastasis. There was no difference in survival between patients with brain metastasis from papillary or follicular thyroid carcinoma.

We introduce a series of twisted donor-acceptor (D-A) carbazole-benzophenone based electroactive bipolar derivatives that were synthesized through the reaction of 4-fluorobenzophenone with various partially alkylated 3,3’-bicarbazoles. The comprehensive structural characterization of these compounds is provided. These amorphous materials exhibit suitable glass transition temperatures ranging from 57 to 102 °C and demonstrate high thermal stability, with decomposition temperatures reaching 400 °C. Moreover, the developed materials exhibit elevated photoluminescence quantum yields (PLQY) of up to 75.5% and favorable HOMO-LUMO levels, along with suitable triplet-singlet state energy values. Due to their good solubility and suitable film-forming properties, all the compounds were evaluated as blue emitters dispersed in 4,4’-bis(N-carbazolyl)-1,10-biphenyl (CBP) host for the fabrication of organic light-emitting diodes (OLEDs) in concentration dependent experiments. Among these experiments, the device containing 15 wt% of the guest 4-(9’-{2-ethylhexyl}-[3,3’]-bicarbazol-9-yl)benzophenone demonstrated the best characteristics, achieving maximum brightness of 3581 cd/m2, current efficiency of 5.7 cd/A, power efficiency of 4.1 lm/W and external quantum efficiency of 2.7%.

The review explores the therapeutic potential of mangrove plants as sources of bioactive compounds, particularly focusing on their anti-inflammatory properties. Mangroves, found in tropical and sub-tropical tidal coasts, exhibit unique ecological and biological activities. The review compiles and examines 136 research findings published between 1982 and 2018, with 41 studies specifically addressing the anti-inflammatory properties of mangroves in Indian coastal regions, including the Andaman and Nicobar Islands. It summarizes the chemical structures, molecular weights, formulas, solvents, and biological activities of these mangroves, as reported by various researchers over time. The data underscore the significant potential of tropical Indian mangroves in anti-inflammatory applications. However, a notable research gap exists regarding the extraction of bioactive compounds from mangrove species in the Andaman and Nicobar Islands compared to other regions such as Gujarat, Maharashtra, Goa, Karnataka, Kerala, Tamil Nadu, Andhra Pradesh, Odisha, West Bengal, and Puducherry. Overall, the compilation provides valuable insights into mangrove-based studies for drug discovery research, emphasizing the need for further exploration and exploitation of these natural resources.

Global warming may increase the potential evapotranspiration (Etp), thereby affecting the amount of clean water resources available in a region. In this study, the systematic biases in temperature outputs of 24 global climate models (GCMs) under 3 emission scenarios are corrected by using 8 bias correction methods. The trend of Etp in Yangzi River Delta in the 21st century is projected by using 4 Etp calculation formulas. The uncertainty of the projections is estimated and decomposed by using multi-way analysis of variance. The influence of uncertainty on the projected change signal is quantified by using the signal-to-noise ratio. The results show that, relative to the reference period (1971~2000), the annual mean daily Etp in Yangzi River Delta will increase by 0.14~0.17mm/d during the period 2021~2050 and by 0.21~0.41mm/d during the period 2061~2090, respectively. During 2021~2050, the uncertainty of Etp increase projections is dominantly contributed by the main effects of GCM (63%) and Etp calculation formula (24%). During 2061~2090, it is mainly contributed by the main effect of GCM (36%), followed by the main effects of emission scenario (34%) and Etp calculation formula (18%). The increase projections of Etp are generally reliable and robust during the two projection periods.

We discuss a central concept of nanothermdynamics; the subdivision potential. We explain how it can be measured or calculated for some typical ensembles, as this has been disputed in the literature. We proceed to discuss its meaning for particular systems, and predict scaling laws for three ensembles. The laws depend on the small system geometry in a predictable way for an ideal gas model with surface adsorption. We provide new equations which relate the subdivision potential to experimental investigations, and give expressions for grand canonical ensembles of spheres, cylinders, slit pores and fluids confined in porous media. The subdivision potential is not compatible with the popular Hadwiger theorem in geometry, and can therefore not be described by a Minkowski set of variables. It is equivalent to Gibbs descriptions when shape- and size variables are defined.

During the last years there has been a high interest in the development of new purely-organic single-component conductors. Very recently, we have reported a new neutral radical conductor based on the perchlorotriphenylmethyl (PTM) radical moiety linked to a monopyrrolo-tetrathiafulvalene (MPTTF) unit by a -conjugated bridge (1). Interestingly, this system behaves as a semiconductor with high conductivity and small energy gap under high pressure. With the aim of developing a new material with improved conducting properties, we have designed and synthesized the radical dyad 2 which was functionalized with an ethylenedithio (EDT) group in order to improve the intermolecular interactions of the TTF subunits. The physical properties of the new radical dyad 2 were studied in detail in solution to further analyze its electronic structure as well as its potential use as radical conductor in the solid state.

The pharmacological effects of the fruiting body of Ophiocordyceps sinensis (Os) exerted antioxidant, anti-virus, and immunomodulatory, whereas the anti-inflammatory effects and active components of Os mycelial submerged culture (OMSC) are not known. This study aimed to investigate the active compounds in the fermented liquid (FLOS), hot water (WEOS), and 50-95% (EEOS-50, EEOS-95) ethanol extracts of OMSC and their anti-inflammatory effects and potential mechanisms in LPS-stimulated microglial BV2 cells. The results demonstrated that all of the OMSC extracts could inhibit NO production in BV2 cells. EEOS-95 exhibited the strongest inhibitory effects (41 % inhibitory ability at 500 µg/mL), and its ergosterol, GABA, total phenolic, and total flavonoid contents were significantly higher than those of the other extracts (18.60, 18.60, 2.28, and 2.14 mg/g, p &lt; 0.05, respectively). EEOS-95 also has a strong inhibitory ability against IL-6, IL-1β and TNF-α with IC50 of 617, 277 and 507 µg/mL, respectively, which is higher than that of 1 mM melatonin. The anti-inflammatory mechanism of EEOS-95 seems to be associated with up-regulation of PPAR-γ/Nrf-2/HO-1 antioxidant-related expression and down-regulation of NF-κB/COX-2/iNOS pro-inflammatory expression signaling. Therefore, we hypothesized that EEOS-95 can prevent neurodegenerative diseases, but the effect on the application in vivo should be further investigated.

Bronchiolitis is an acute viral infection of the lower respiratory tract that affects infants and young children. Respiratory syncytial virus (RSV) is the most common causative agent, however other viruses can be the reason of the disease. We retrospectively reviewed the clinical features of infants aged less than 12 months referred to our Pediatric Units of Chivasso, Cirié and Ivrea for acute bronchiolitis requiring hospitalization over two consecutive bronchiolitis seasons. Patient-, disease- and treatment related variables were analyzed in this retrospective study. We were able to show how with the high flow oxygen support (HFNC) only a very low number of children (8 out of 192) need to be trasferred to our HUB referral centers. The probability of success were 96% for all patients and 93% for RSV vs. 98% for non-RSV patients (P=NS). Factor associated to failure of treatment were age below 1 months and the failure of HFNC. The wide and increasing use of HFNC in pediatric inpatients improved management of bronchiolitis in Spoke hospitals, reducing transfer to a Hub hospital provided with Intensive Care Units.

Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicles (EVs) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by atomic force microscopy, western blot (WB), nanoparticle tracking analysis and label-free proteomics. Fresh PBMCs from healthy donors were treated with PC- or control-derived heterologous EVs followed by flow cytometry analysis of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated, or -untreated PBMCs was performed and IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by proteomic analysis were connected in a single functional network (p=1x10-16) and were involved in “Immune System” (FDR: 1.10x10-24 and 3.69x10-19, respectively). Interestingly, treatment of healthy donor-derived PBMCs with Capan-2 EVs, but not with BxPC-3 EVs or heterologous control EVs induced early activation of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among major upstream regulators, as confirmed by ELISA. Proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune response, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.

The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. We have now investigated all bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies with minodronate could be valuable.

A burgeoning body of scholarship identifies and discusses botanic gardens as increasingly important centres of biodiversity conservation and sustainability. Notwithstanding the high quality and richness of this literature, it encompasses relatively autonomous fields of expertise that are neither designed nor expected to promote cross-disciplinary, integrative, accounts of botanic gardens as institutions of conservation and sustainability. Bridging key aspects of the botanic garden literature, this article brings into conversation historical accounts with contemporary scholarship on the matter. In so doing, it unveils dilemmas and challenges faced by botanic gardens as they grapple with their historic legacies, but also renew their relevance in nurturing sustainable socio-environmental futures. The article proceeds by covering three focal points. First, it summarizes the scholarly literature on the history of botanic gardens. Second, it presents accounts of current scientific and biodiversity conservation endeavours as reflexive engagements with their historical legacies. Third, it addresses the recent emergence of socio-cultural missions at botanic gardens as a significant step beyond their historical focus on plants and plant ecosystems.

Background: Cochlear implantation is an efficient treatment for postlingually deafened adults who do not benefit sufficiently from acoustic amplification. Implantation is indicated when it can be foreseen that speech recognition with a cochlear implant (CI) is superior to that with a hearing aid. Especially for subjects with residual speech recognition it is desirable to predict CI outcome on the basis of preoperative audiological tests. Purpose: The purpose of the study was to extend and to refine a previously developed model for CI outcome prediction for subjects with preoperative word recognition to include subjects with no residual hearing by incorporat-ing additional results of routine examinations. Results: By introducing the duration of unaided hearing loss (DuHL) the median absolute error (MAE) of the prediction was reduced. While for subjects with preoperative speech recognition the model modification did not change the MAE, for subjects with no residual speech recognition before surgery, the MAE decreased from 23.7% with the previous model to 17.2% with the extended model. Conclusions: Prediction of word recognition with CI is possible within clinically relevant limits. Outcome prediction is particu-larly important for preoperative counselling and in CI aftercare, to support systematic monitor-ing of CI fitting.

Intracellular aggregates of the alpha-synuclein protein result in cell loss and dysfunction in Parkinson’s disease and atypical parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as alpha-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby alpha-synuclein aggregates in turn mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of alpha-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of alpha-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunnelling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which alpha-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.

(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At present, the exploration of novel therapies for alleviating diabetic neuropathy-associated pain is genuinely captivating, considering that current therapeutic options are characterized by poor efficacy and significant risk of side effects. In the current research, we evaluated the antihyperalgesic effect of sildenafil (phosphodiesterase-5 inhibitor) – metformin (antihyperglycemic agent) combination and its impact on biochemical markers in alloxan-induced diabetic neuropathy in rats; (2) Methods: The study comprised a cohort of 70 diabetic rats and 10 non-diabetic rats which were submitted to hot, cold, and tactile stimulus tests. Morover, we investigated the influence of this combination on TNF-α, IL-6 nitrites and thiols levels in brain and liver tissues; (3) Results: The results demonstrated that all sildenafil-metformin combinations decreased the pain sensitivity in von Frey test, Hot-plate test and Cold-plate test. Furthermore, alterations in nitrites and thiols concentrations and pro-inflammatory cytokines (specifically TNF-α and IL-6) were noted following a 15-day regimen of various sildenafil-metformin combinations. (4) Conclusions: The combination of sildenafil and metformin has a synergistic effect in alleviating pain in alloxan-induced diabetic neuropathy rats. Additionally, the combination effectively decreased inflammation, inhibited the rise in NOS activity, and provided protection against glutathione depletion.

To assess the community health workers’ (CHWs) knowledge, attitude, and practices (KAP) in type-2 diabetes (T2D) and hypertension (HTN) management. We thus also sought to assess the potential health system barriers for incorporating CHWs in T2D and HTN management. Mixed-method study comprised (1) a survey among 153 active CHWs to assess their KAP of T2D and HTN, and (2) semi-structured interviews with key informants to understand challenges of the health system and proposed solutions in incorporating CHWs in T2D and HTN management. The majority of CHWs correctly answered general knowledge questions on NCDs, risk factors, and prevention; however, only one-quarter correctly answered questions on smoking, family history, or tobacco use as risk factors. Most respondents appeared to have positive attitudes and have been practicing some activities related to T2D and HTN. Both financial and non-financial resource constraints were cited as challenges of the health system; therefore, re-structuring the role definition of CHWs and task of responsibilities, and assessment the need and workload have been proposed as ways forwards to effectively incorporate CHWs in T2D and HTN care. CHWs in Cambodia have shown their potential in T2D and HTN management; however, a well-designed strategy including technical training, clearly defined roles and responsibilities, and strong supporting structure are important to maximize their potential in the health system.

Obesity poses significant challenges in rural communities worldwide due to limited resources and healthcare access. Practical, innovative, and culturally sensitive approaches are essential. Time-Restricted Eating (TRE), aligning food intake with circadian rhythms, emerges as a promising strategy. By restricting eating to specific time windows, TRE synchronizes with the body's internal clock, offering potential metabolic health benefits. This review examines TRE's potential in rural obesity management, highlighting its simplicity and scalability. While TRE may address rural health disparities, cultural considerations and challenges such as undernutrition must be acknowledged for effective implementation. Overall, TRE shows promise in improving metabolic health and well-being in rural populations.

Concrete contributes 8% of all global carbon emissions making the need to find substitute critical for environmental sustainability. Research has indicated the potential for recycled plastics to be used as concrete substitutes. This study extends existing research by investigating the use of polycarbonate (PC) in plastic sand bricks as a mechanical equivalent to concrete. PC has high compressive strength, durability, impact strength, thermal resistivity, clarity, fatigue resistance, and UV resistance. This work provides a method and mold to produce a matrix of sand-plastic sample compositions with dimensions adhering to ASTM D695 standard for compressive properties of rigid-plastic. Compositions of 0% (control), 20%, 30%, 40%, and 50% sand by weight were tested. Samples were tested for compressive strength until yield and stress-strain behaviors plotted. The results for 100% PC demonstrated an average and maximum compressive strength of 71 MPa and 72 MPa, respectively. The 50% PC and 50% sand composition yielded an average and maximum compressive strength of 71 MPa and 73 MPa respectively with an increase in compressive stiffness, and transition to shear failure resembling cement. With a composite density of 1.86 g/cm3 against concrete’s average 2.4 g/cm3, and a compressive strength exceeding commercial concrete demands of 23.3 MPa to 30.2 MPa, this lightweight alternative meets the strength demands of concrete, reduces the need for new construction materials, and provides an additional recycling opportunity for nonbiodegradable waste plastic.

Introduction: Nephrotic syndrome (NS) remains the most frequent mode of presentation of glo-merular diseases in children; in addition, the NS is primitive, i.e., idiopathic in 90% of cases with an average age of onset between 2 and 10 years. The objective of our study was to describe the char-acteristics and outcome of NS in children from 3 major hospitals from one of the poorest countries worldwide (Chad). Patients and Methods: Observational, cross-sectional, descriptive and multicenter study which took place over a period of 36 months (January 1,2019-December 31,2021) carried out in 3 hospitals in N’Djamena (Chad). All children aged 1-15 years presenting with NS were included. Results: Out of 16,776 children hospitalized or followed-up in outpatient clinics, 24 cases of NS were identified, giving a prevalence of 0.14%. The median age at presentation was 6.16(1-10) years. Nineteen children were male (sex ratio 3.8). There were 8 impure NS (33.3%). Edema was present in all patients, oliguria in 29.16%(n=7), and arterial hypertension in 20.83%(n=5) of cases. Mean proteinuria, albuminemia and total proteins were 2.86g/L, 19.13g/L and 30.41g/L respectively. Median serum creatinine was 87.3 µmol/L(75-1375µmol/L); three patients had acute renal failure on admission. Four patients had secondary NS. All patients (n=20) with idiopathic NS had received corticosteroid therapy; steroid-sensitivity was found in 90% of patients. Those who were not ster-oid-sensitive or relapsed underwent kidney biopsy (n=7); the most represented histological lesion was focal segmental glomerulosclerosis (FSGS; n=4), followed by minimal change disease (n=2), and membranoproliferative glomerulonephritis (n=1). The median length of hospitalization stay was 10.67 (5-27) days. None of the patients with idiopathic NS died. At last follow-up sixteen patients (80%) achieved long-term complete remission with normal renal function; however, 4 had subse-quent relapses. 16 patients. One patient with secondary NS died. Conclusion: In Chad childhood idiopathic nephrotic syndrome involves mostly young male; steroid sensitivity is as high as 95% and in the long-term 80% of the patients are in remission with normal renal function.

Plant leaf area index (LAI) is a key characteristic affecting field canopy microclimate. In addition to traditional professional measuring instruments, smartphone camera sensors have been used to measure plant LAI. However, when smartphone methods were used to measure conifer forest LAI, very different performances were obtained depending on whether the smartphone was held at the zenith angle or at a 57.5° angle. To validate further the potential of smartphone sensors for measuring conifer LAI and to find the limits of this method, this paper reports the results of a comparison of two smartphone methods with an LAI-2000 instrument. It is shown that both methods can be used to reveal the conifer leaf-growing trajectory. However, the method with the phone oriented vertically upwards always produced better consistency in magnitude with LAI-2000. The bias of the LAI between the smartphone method and the LAI-2000 instrument was explained with regard to four aspects that can affect LAI: gap fraction, leaf projection ratio, sensor field of view (FOV), and viewing zenith angle (VZA). It was concluded that large FOV and large VZA cause the 57.5° method to overestimate the gap fraction and hence underestimate conifer LAI, especially when tree height is greater than 2.0 m. For the vertically upward method, the bias caused by the overestimated gap fraction is compensated for by an underestimated leaf projection ratio.

Children under two years old are at risk for anemia because young children have an increased need for iron for their physical growth and brain development. The purpose of this study was designed to evaluate the effects of a caregiver potential support program on anemia prevention in children six months to two years old attending the subdistrict health-promoting hospital in Thasala District, Nakhon Si Thammarat Province. This study was quasi-experimental. The sample included children aged six months to two years old and their caregivers, who were selected by random sampling and allocated to either the experimental or control group, with 40 pairs per group. The experimental group received a potential support program, while the control group received regular care. Both groups were followed for 12 weeks. The instruments used were the potential caregiver assessment, children’s anemia assessment, and a program to support the potential of primary caregivers. Descriptive statistics, chi-square, and t-tests were used to analyze the data. The results revealed that 11.4% of the children had anemia, and a hematocrit count of less than 33% (range = 30-40, M = 34.89, SD = 1.97). The mean scores of knowledge about anemia and iron supplementation after using the program in the experimental group and control group were significantly different (p < 0.001). The mean scores of knowledge about anemia in the experimental and control group were 15.75, SD = 0.54, and 13.28, SD = 1.43 respectively. The mean scores of knowledge about iron supplementation in the experimental and control group were 10.75, SD = 0.49, and 8.15, SD = 1.54 respectively. It was found that the experimental group had a higher mean score on food care behaviors than the control group for 6-11 months and 1-2 years, with statistical significance. The experimental group also had a higher mean score of care behaviors concerning children’s consumption of medicine than the control group (M = 58.20, SD = 4.05; M = 45.78, SD = 9.66, respectively), (p < 0.001). The mean score of the hematocrit level for the experimental group was found to be higher than the control group after receiving the program (M = 35.80, SD = 1.55; M = 34.83, SD = 2.14, respectively), (p < 0.05). Therefore, healthcare providers should support caregivers' capacity to provide continued care for children to prevent anemia.

Responding to changing value creation processes in the sheet metal working sec-tor, where the complexity and interchangeability of products challenge traditional dif-ferentiation strategies, this empirical analysis explores integrating service-oriented and data-driven business models as new paths to ensure competitiveness, especially for small and medium-sized enterprises (SMEs). This study aims to capture the current state and challenges associated with the implementation of these business models in this sector. The research was conducted through semi-structured interviews with SMEs in the industry. The findings indicate that service-oriented and data-driven business models are not yet widely adopted and that manufacturing companies re-quire support in their implementation. Fields of action were identified for the industry. These are "Creating awareness and understanding", "Recognizing added value", "In-creasing company maturity" and "Understanding the change process". Cooperation between science and industry is essential in tackling these fields of action to ensure the successful integration of such business models in manufacturing companies. This pa-per identifies challenges in the fields of action that companies must address through a structured approach promoting awareness, recognizing value, improving organiza-tional maturity, and understanding the change process to successfully implement ser-vice-oriented and data-driven business models.

Lumpy skin disease (LSD), caused by a virus within the Poxviridae family and Capripoxvirus genus, induces nodular skin lesions in cattle, spreading through direct contact and insect vectors, significantly affecting global cattle farming. Despite available vaccines, their effectiveness is limited by poor bioavailability and adverse effects. Our study aimed to identify potential inhibitors targeting LSD-associated DNA polymerase protein, selecting LSDV039 for further investigation through comprehensive analysis and computational methods. Virtual screening revealed rhein and taxifolin as potent binders among 380 phytocompounds, with respective affinities of -8.965 and -7.195 kcal/mol. Canagliflozin and tepotinib exhibited strong affinities (-9.858 and -8.856 kcal/mol) among 718 FDA-approved antiviral drugs. Molecular dynamics simulations of canagliflozin, tepotinib, rhein, and taxifolin highlighted taxifolin's superior stability and binding energy. Rhein displayed compactness in RMSD and RMSF but fluctuations in Rg and SASA, while canagliflozin demonstrated stability compared to tepotinib. The study highlights the promising potential of repurposed drugs and phytocompounds as LSD therapeutics. However, extensive validation through in-vitro, in-vivo, and clinical trials is crucial for their practical application.

The term “conservation,” as it relates to biodiversity in a Western context, has a storied past and as conservation science and societal values have evolved, consensus over its precise meaning has remained elusive. The broad scope of contemporary definitions hampers effective communication during a period of environmental crisis and is troublesome for any derivative concept which aims to empirically quantify the efforts of the conservation sector. This presents an avoidable hindrance to the systematic planning of the conservation field. To help remedy this situation, we provide an outcome separation framework that is based on the expected degree of separation between an action’s proximate outcome, from its intended, ultimate outcome for a habitat and/or species. Framing a definition of conservation through this lens of outcome separation allows for conservation-related actions to be clearly categorized into one of three discrete tiers: primary, secondary, and tertiary. A distillation of this tiered framework also provides a new definition of biodiversity conservation that is more rigorous and adaptable to future conceptual evolutions of the field.

Background: Membranous glomerulonephritis (MGN) is one of the most common causes of nephrotic syndrome in non-diabetic adults, accounting for up to one-third of biopsy diagnostics in some regions. A watchful waiting strategy has been adopted to accurately assess the success of MGN. In this study, we predict prognostic risk factors for primary MGN patients for effective intervention and prognosis. Materials and Methods: This is a retrospective study design involving 125 biopsy-proven MGN subjects on follow-up from January 2012 to October 2019 in Hospital Serdang and Hospital Kuala Lumpur, Malaysia. Result and Conclusion: After the median follow-up of 36 (15.0-57.0) months, 26 (20.8%) consisting of 17 (13.6%) primary MGN and 9 (7.2%) secondary MGN subjects achieved complete remission while 17 (13.6%) and 10 (8.0%) of primary and secondary MGN subjects respectively achieved spontaneous remission. Subjects with nephrotic range proteinuria have 2.917 odds more at risk of primary MGN while subjects with hypertension have 2.417 odds risk of primary MGN compared to those with no hypertension at presentation. Multiple logistic regression models retained only factors directly associated with MGN with only nephrotic range proteinuria associated with primary MGN. Those with nephrotic range proteinuria were 3.04 times the odds of primary MGN when compared with those without nephrotic syndrome (95% C. I = 1.089, 8.472). The nephrotic syndrome could be used to determine the prognosis in patients with primary MGN especially those at risk of end-stage kidney disease.

Much research has been conducted to determine how hair regeneration is regulated, as this could provide therapeutic, cosmetic, and even psychological interventions for hair loss. The current study focused on the hair growth effect and effective utilization of fatty oil obtained from Bryde's whales through high-throughput DNA microarray approach in conjunction with immunohistochemical observations. The research also examined the mechanisms and factors involved in hair growth. In an experiment using female C57BL/6J mice, the vehicle control group (VC: propylene glycol: ethanol: water), the positive control group (MXD: 3% minoxidil), and the experimental group (WO: 20% Whale Oil) were topically applied to the back of the mouse. The results showed that 3% MXD and 20% WO were more effective than VC in promoting hair growth, especially 20% WO. Furthermore, in hematoxylin and eosin-stained skin tissue, an increase in the number of hair follicles and subcutaneous tissue thickness was observed with 20% WO. Whole-genome transcriptomic analysis also showed that 20% WO may have lower stress- and inflammation-related responses than 3% MXD. Therefore, whale oil can be expected to be used as a safe hair growth agent.

Leishmaniasis are neglected diseases that affect regions such as South Asia, South Africa and Latin America, less developed regions. Current treatment, for cutaneous, mucocutaneous and visceral leishmaniosis, which are the main forms of the disease, is based on the administration of pentavalent antimonial and amphotericin B. However, these drugs have low efficacy and high toxicity. For this reason, the search for new treatments for this disease is necessary, based on studies of new molecules and their conformations. The research proposed the conformational study of brominated guanidine compounds with potential antileishmanial activity using Nuclear Magnetic Resonance (NMR) and X-ray diffraction (XRD) techniques. The present study involves the bro-minated molecules, LQOF-G2, LQOF-G30, LQOF-G35 and LQOF-G35-Br. The later was synthesized by the reaction of LQOF-G35 with NBS under IR irradiation at 120 Watts of potency and dichloro-methane as solvent by 12-h of exposition. The obtained results demonstrated the efficiency of the bromination method, since two bromines atoms entered the molecule. Furthermore, NMR analysis showed the occurrence of a conformational change from Z to E when compound LQOF-G35 was brominated to LQOF-G35-Br. This feature was well confirmed by comparative DRX study of the LQOF-G35 and LQOF-G35-Br compounds. The antileishmanial activity of LQOF-G2 e LQOF-G35 motivated the synthesis of new brominated compounds LQOF-G30 e LQOF-G35-Br.

Postprandial glucose levels between 4 and 7.9 hours (PPG4–7.9h) correlate with mortality from various diseases including hypertension, diabetes, cardiovascular disease, and cancer. This study aimed to assess if predicted PPG4–7.9h could diagnose diabetes. Two groups of participants were involved: Group 1 (4420 participants) had actual PPG4–7.9h, while Group 2 (8422 participants) lacked this measure but had all the diabetes diagnostic measures. Group 1 underwent multiple linear regression to predict PPG4–7.9h using 30 predictors, achieving accuracy within 11.1 mg/dL in 80% of the participants. Group 2 had PPG4–7.9h predicted using this model. Receiver operating characteristic curve analysis showed that predicted PPG4–7.9h could diagnose diabetes with an accuracy of 87.3% in Group 2, with a sensitivity of 75.1% and specificity of 84.1% at the optimal cutoff of 102.5 mg/dL. Simulation on 10,000 random samples from Group 2 revealed that 175 participants may be needed to investigate PPG4–7.9h as a diabetes diagnostic marker with a power of at least 80%. In conclusion, predicted PPG4–7.9h appears to be a promising diagnostic indicator for diabetes. Future studies seeking to ascertain its definitive diagnostic value might require a minimum sample size of 175 participants.

Based on the Flashing Ratchet Potential (FRP) and Electro-Spectroscopy detection techniques, a new detection method was experimentally examined. This method allows the detection of sub-micro particles in the human exhaled air such as viral particles and other biological agents. The detection signal created by this method is carried out by electron current buildup forming an Electric Current-Spectrum (ECS) distinguishing the contents of the exhaled air samples. The detection method was developed based on FRP and a beam of free charges passing through the electrodes of the FRP. The ECS is characterized by low-energy free charges interacting with the medium through which they pass, where numerous free charges are scattered (delayed) as a result of these interactions. The resulting ECS is characterized by FRP's capacity to drift back the delayed free charges to their original starting positions. By comparing the ECS of two exhale air samples, this new technology can be utilized to identify the presence of viral and microorganisms’ particles. The time-escalating ECS difference quickly indicates the presence of such particles. Moreover, the FRP's optimal operating settings was experimentally defined, in addition to the experimental evaluation of its functionality to confirm the FRP's promising sensing capabilities, which were statistically examined several times to ensure the reproducibility of the results.

The doctoral defense is an important step towards obtaining the doctoral degree. As such, preparing for the event is necessary. Anecdotal evidence highlights that there is a wide variety of ways in which doctoral candidates prepare for the defense. In this work, I want to explore if there is a relation between the way in which a doctoral candidate prepares for the defense and two important aspects of the defense: the outcome of the defense, and the student perception during and after the defense. For this purpose, I first reviewed the literature on the topic of the preparation for the doctoral defense. Then, I carried out an international survey on the doctoral defense and analyzed the data of the 204 completed surveys with respect to the preparation for the defense using quantitative and qualitative methods. The methods I used included the statistical tests of the correlation between on one hand the preparation and on the other hand the defense outcome and student perception. I used inductive thematic analysis of the open-ended survey questions to gain deeper insight in the way candidates prepared for their defense. I found that candidates most often prepare by making their presentation, reading their thesis, and practicing. The most effective measure is the mock defense, followed by a preparatory course. Reading blogs, books, and chapters is a less effective preparation measure. The conclusion of this work is that doctoral candidates need to understand the format of their defense in order to be able to prepare properly, and that universities should explore either individual pathways to the defense or pilots using a mock defense and/or preparatory course to give their doctoral candidates the necessary tools to prepare for their doctoral defense.

Abstract Background: Atrazine, a widely used herbicide, is recognized for its potential endocrine-disrupting effects, though its direct link to diabetes has not been extensively studied. Objectives: This study investigates the relationship between atrazine exposure and diabetes incidence, especially in agricultural settings, and examines how socioeconomic factors like income and education levels influence diabetes risk. Methods: A retrospective cohort study was conducted using data from 67 counties in Pennsylvania from 2011 to 2019. Atrazine exposure was measured in local water sources and correlated with diabetes data from the Pennsylvania Behavioral Risk Factor Surveillance System (BRFSS). Socioeconomic data were sourced from U.S. Census Bureau records, with logistic regression used to adjust for confounders such as age, race, and lifestyle. Results: Findings showed a significant association between high atrazine exposure and increased diabetes incidence, even after adjusting for confounders. Discussion and Conclusion: The study highlights a significant health risk posed by atrazine, particularly for socioeconomically disadvantaged groups. It underscores the need for stricter atrazine regulation and public health interventions to mitigate its impact. Further research is crucial to understand how atrazine affects glucose metabolism and diabetes development. Implementing stricter environmental controls and educational initiatives could reduce the diabetes burden in impacted communities.

Dementia is a rising public health concern. Feeding and nutritional problems increase as the disease progresses, affecting clinical course and caregiver burden. While some guidelines advise against percutaneous endoscopic gastrostomy (PEG) and tube feeding in advanced dementia, conflicting evidence exists. This study aims evaluating nutritional status and the influence of PEG-feeding on outcome and evolution of nutritional/progonosis markers of patients with severe dementia (PWSD) who underwent gastrostomy for nutritional support. We conducted a 16-year rectrospective study on 100 PEG-fed PWSD with strong familiar support. We evaluated survival PEG-feeding period, safety, and objective nutritional/progonosis data at the gastrostomy day and after 3 months: Body Mass Index (BMI), Mid Upper Arm Circumference, Tricipital Skinfold, Mid-Arm Muscle Circumference, albumin, transferrin, total cholesterol and hemoglobin. Most patients presented low values in these nutritional/progonosis parameters. No major life-threatening PEG complications were reported. The mean survival time after gastrostomy was 27.9 months (median of 17 months). Female sex, BMI recovery at 3 months, and higher baseline hemoglobin levels were associated with a reduced risk of death and increased survival time. The study concluded that, in carefully selected PWSD with strong familiar support, PEG feeding can improve nutritional status and have a positive impact on survival.

Background: It is well known the adverse effect of mercury exposure on pregnant women and newborns. Interactions between environmental factors and individual genetic susceptibility have been identified, particularly polymorphisms of codifying genes for the Glutathione S-transferase family (GSTs). Herein, we report a case series of patients with high Hg levels in biosamples. Case Series: Fourteen cases with high Hg levels were identified. Non-occupational or home exposure risk factors were identified. All mothers reported fish consumption during pregnancy. Almost 60% of the individuals were null for either one GSTs gene. To date, in the subsequent mother-child pairs toxicology controls no signs or symptoms of poisoning were identified and most of the mercury levels decreased and are below the accepted limit. Discussion: In this case series we found some similarities with the literature; among them, the relation of Hg ratio in maternal blood and umbilical cord, a possible exposure factor is the consumption of fish during pregnancy and, the high levels of Hg may be related with susceptibility biomarkers such as GSTs gene polymorphisms. This case series highlights the need to develop studies that evaluate the interactions between environmental factors and individual genetic susceptibility. Additionally, the importance of evaluating which Colombian fish species present the highest levels of Hg.

Osteosarcopenic obesity (OSO) is described by the simultaneous presence of osteopenia/osteoporosis, sarcopenia, and increased adiposity. Over time, older adults with OSO syndrome might be at greater risk for loss of physical function and bone fractures. Furthermore, a sedentary lifestyle, inadequate nutrition, pharmaceutical drugs and chronic conditions encompass the multifactorial nature of OSO syndrome. Physical activity and a healthy diet play a crucial role in management and treatment of OSO syndrome. Research has shown that even low-intensity physical activity or daily habitual activity can maintain bone mineral density, muscle strength and improve muscle quality, and reduce adiposity. However, older adults with high risk of fall and injuries require tailored exercise intensity. Also, balanced daily intake of vitamin D, calcium and protein is important in prevention and treatment of OSO syndrome in postmenopausal women. Effective measurement of bone mass, muscle mass and strength is required when detecting OSO syndrome and to evaluate the balance, strength and endurance of elder individuals and severity of the condition.

Scientific studies on the impact of wood species on solid fuel production, performance, and sustainability are grossly inadequate. The knowledge of this is imperative as users of solid fuels are increasing rapidly, especially in Africa. On this note, it becomes necessary to explore measures that will improve its efficiency and sustainability as an energy source. This study investigates some properties of selected wood species used as an energy source in Nigeria and their pelleting potential. Nine (9) samples were characterized and assessed for suitability of pelleting following four wood pellet quality standards. The findings revealed Anogeissus leiocarpus as the species with the best rating score in terms of fuel properties while Vitellaria paradoxa as the lowest. However, in terms of conformity with the four wood pellets standards, Khaya senegalensis, Parkia biglobosa and Anogeissus leiocarpus having presented density, calorific value, sulfur, arsenic, cadmium, and lead within the limits of the wood pellet quality standards were considered the best wood species in terms of fuel suitability and pelleting potential. The findings therefore suggest that not all wood species are suitable as fuel. Thus, for species that do not meet the standard wood pellet requirements, alternatives such as the use of biomass blends, additives, or process adjustments can be employed to adapt the quality to the standards or by using the fuels in improved cookstoves.

Background: Learning arrangements in health care profession education are increasingly taking place in digital environments. VR in nursing education, as one of the digital elements, is the subject of controversial debate. On the one hand it supports the authenticity of case studies by adding realistic perspectives and information. On the other hand, the costs of developing and maintaining software and hardware hinder long-term implementation. Methods: In this paper, we describe our findings and insights from two different research projects focused on the incorporation of digital tools, particularly virtual reality (VR), into nursing education. Based on the German context, our aim is to promote the adoption of innovative digital methods in nursing education and to offer invaluable experiences from the field. Results: Starting with a brief recapitulation of the projects, we then elucidate the pedagogical strategies for embedding VR-driven scenarios in nursing education. Based on our experiences during the projects we identify various positive aspects, such as change of perspective and simulating acute situations. Key findings: Although potential drawbacks remain, we advocate long-term implementation and specific use of VR at the interface between theory and practice. Nevertheless it is crucial to establish regular evaluation observing the value of digitalisation, especially VR; for nursing education.

Sarcopenia is an age-related condition that involves a progressive decline in muscle mass and function, leading to increased risks of falls, frailty, and mortality. Although the exact mechanisms are not fully understood, aging-related processes like inflammation, oxidative stress, reduced mitochondrial capacity, and cell apoptosis contribute to this decline. Disruption of the circadian system with age may initiate these pathways in skeletal muscle, preceding the onset of sarcopenia. At present, there is no pharmacological treatment for sarcopenia, only resistance exercise and proper nutrition may delay its onset. Melatonin, derived from tryptophan, emerges as an exceptional candidate for treating sarcopenia due to its chronobiotic, antioxidant, and anti-inflammatory properties. Its impact on mitochondria, organelle where it is synthesized and crucial in aging skeletal muscle, further highlights its potential. In this review, we discuss the influence of clock genes in muscular aging, with special reference to peripheral clock genes in the skeletal muscle, as well as their relationship with melatonin, which is proposed as a potential therapy against sarcopenia.

To understand the mystery of final unification, in our earlier publications, we proposed that there exist three atomic gravitational constants associated with electroweak, strong and electromagnetic interactions. During cosmic evolution, if one is willing to give equal importance to Higgs boson and Planck mass in understanding the massive origin of elementary particles, then it seems quite logical to expect a common relation in between Planck scale and Electroweak scale. Based on these two points, we noticed that, electroweak field seems to be operated by a primordial massive fermion of rest energy 585 GeV. It can be considered as the zygote of all elementary particles and galactic dark matter. H-bar seems to be a characteristic outcome of unified electroweak gravity. Electron rest mass seems to be a characteristic outcome of electroweak and strong gravity. Proton rest mass seems to be a characteristic outcome of electroweak, strong and electromagnetic gravity. Recently observed 3.5 keV photon seems to be an outcome of annihilation of charged baby lepton of rest energy 1.75 keV. Interesting point to be noted is that, Schwarzschild radius of electron is 0.48 nanometer and it needs further investigation with respect to emerging nano-science and technology. Proceeding further, by considering electromagnetic and weak gravitational constants, neutron life time can be understood.

Clusterin (CLU) protein is involved in various pathophysiological processes including carcinogenesis and tumor progression. In recent years, the role of the secretory isoform has been demonstrated in tumor cells, where it inhibits apoptosis and favors the acquisition of resistance to conventional treatments used to treat cancer. To determine the possible therapeutic potential of inhibiting this protein, numerous studies have been carried out in this field. In this paper, we show the existing knowledge on the inhibition of this protein in different types of cancer and discuss the importance it could have in the development of new therapies directed against this pathology.

Background and Objectives: Intramedullary spinal cord tumors (IMSCT) are rare entities. Especially, a location in the upper cervical spine as a highly eloquent region carries the risk of postoperative neurological deficits, such as tetraparesis or respiratory dysfunction. Evidence for respiratory dysfunction is scarce. The aim of this study was to describe the early and late postoperative clinical course of this highly eloquent tumours. Patients and Methods: This is a single-centre retrospective cohort study. We included 35 patients with IMSCT at levels of craniocervical junction to C4 who underwent surgical treatment between January 2008 and December 2022. The authors analysed the patients' preoperative status, tumour- and surgery-specific characteristics, and follow-up functional status. Results: The study cohort included 22 patients with grade II ependymoma (62.9%), 2 low-grade astrocytomas (5.7%), 2 glioblastomas (5.7%), 6 hemangioblastomas (17.1%), 2 metastases (5.7%), and 1 patient with partially intramedullary schwannoma (2.9%). Gross total resection was achieved in 76% of patients. Early dorsal column related symptoms and motor deterioration occurred in 64% and 44% of patients, respectively. At a follow-up of 3.27 ± 3.83 years, 43% and 33% of patients preserved postoperative sensory and motor deterioration, respectively. The median McCormick Scale grade was 2 in the preoperative and late postoperative periods, respectively (p=0.0897, α=0.05). Only two out of 35 patients (5.7%) developed new intermittent respiratory dysfunction, of whom two were transient. There were no surgery-related deaths. Conclusions: The surgery of IMSCT of the upper cervical spine could be performed without major procedure-related risk. Roughly a half of the patients develop new neurological deficit in the immediate postoperative period. However, most of the patients still maintain functional independence. The rate of respiratory insufficiency is low and is strongly influenced by the rapid neurological deterioration in high-grade tumours.

Lung cancer remains the main cause of global cancer-related deaths. Currently low-dose computed tomography (LD-CT) shows a 20% reduction of mortality. However, its clinical suitability is hindered by cost, radiation, and some false positives. Thus, the discovery non-invasive and less-expensive biomarker is urgent needed. In this scenario, proteins released in biological fluids could be considered interesting biomarkers for their role in cancer development. We conducted a pioneering case-control pilot study aimed at assessing the usefulness of Raf Kinase Inhibitory Protein (RKIP) and its phosphorylated form (pRKIP) as potential early-stage lung cancer biomarkers. Urine and Blood samples of two consecutive and independent cohorts of lung cancer patients and healthy controls were screened by means of a novel experimental ELISA assay designed to evaluate both forms of the biomarker. Although urinary levels of RKIP were not statistically different between the lung cancer group and high-risk healthy group, serum ones instead increased significantly in early stage LC patients and permitted to discriminate LC patients from both low-risk (HS) and high-risk healthy subjects (HR-HS) with an overall 93% accuracy (AUC 0.93) when LC was compared to HS and 74% (AUC 0.73) when it was compared to high-risk group. Of note, the analysis of RKIP/pRKIP ratio also showed a high accuracy (90% - AUC 0.95) in discriminating LC patients from HS and more importantly, it allowed to identify LC patients compared to HR-HS, with a higher accuracy (79% - AUC 0.79) than RKIP alone. We hypothesize that serum RKIP levels may be correlated to the activation of the immune systems against the tumor during the first phases of its development. Our study identified a preliminary, non-invasive, RKIP and pRKIP profile able to discriminate with high specificity and sensitivity the early-stage lung cancer patients from high-risk Healthy Subjects. These results, although preliminary, suggest the utility of measuring RKIP/pRKIP as potential new screening test for lung cancer and provide the basis for future validation studies.

Exosome-based therapy has emerged as a promising strategy for addressing diverse disorders, indicating the need for further exploration of the potential therapeutic effects of the exosome cargos. This study introduces "enhanced exosomes," a novel type of exosomes developed through a novel cell culture system. These specific exosomes may become potent therapeutic agents for treating ovarian disorders. In this study, we conducted a comparative analysis of the protein and miRNA cargo compositions of enhanced exosomes and naïve exosomes. Our findings revealed distinct cargo compositions in enhanced exosomes, featuring upregulated proteins such as EFEMP1, HTRA1, PAM, RSU1, and SDF4, suggesting their potential for treating ovarian disorders. MicroRNA profiling revealed that miR-1-3p, miR-103a-3p, miR-122-5p, miR-1271-5p, miR-133a-3p, miR-184, miR-203a-3p, and miR-206 are key players in regulating ovarian cancer and chemosensitivity by affecting cell cycle progression, cell proliferation, and cell development. We examined polycystic ovary syndrome and premature ovarian insufficiency and identified altered expression of various miRNAs, such as miR-106a-5p, miR-130b-5p, and miR-130b-3p, for diagnostic insights. This study highlights the potential of enhanced exosomes as new therapeutic agents for women's reproductive health, offering a detailed understanding of the impact of their cargo on ovarian disorders.

Pakistan relies mostly on fossil fuel for fulfilling its energy demand which is expensive as 11 well as not friendly for the environment. The need of the hour is to shift from fossil fuels to renew-12 able energy resources like geothermal, wind, solar etc. to cater for global warming issues. Pakistan 13 has a lot of potential geothermal sites because of several fault lines and hot springs. A sound 14 knowledge of ground temperature is essential to use geothermal energy, which is obtained by drill-15 ing boreholes and putting sensors making it an expensive procedure. Thus, to avoid huge cost for 16 drilling bore holes, particularly for ground temperature analysis, a numerical approach has been 17 considered for determining ground temperature. Furthermore, correlation charts between air and 18 ground temperatures have been developed as there were no proper studies on the ground temper-19 ature of Pakistan. Then, with the help of a boreholes drilled in National University of Sciences and 20 Technology Islamabad Pakistan, the actual ground and numerically calculated temperatures have 21 been compared which shows an error margin in the range between 0.27% for higher depths to 7.3% 22 near surface. Thus, it is shown that the proposed method is easy to implement and better than large 23 scale testing methods for the depths at which geothermal energy is extracted.

Herbal Coffee is getting more popular due to its unique flavor and higher concentration of bioactive compounds, mainly polyphenols. Rosemary is a unique herb with potent antioxidant properties. A green technique called ultrasound aids in releasing bioactive substances from the plant cell wall. In this context, ultrasound-assisted herbal coffee prepared and their anti-diabetic, anti-Alzheimer, and antioxidant activities were measured while the LC/MS was used to determine the bioactive components from the herbal coffee infusion. A total of 95 secondary metabolites were putatively reported, including alkaloids, phenolic acids, and flavonoids, which we identified in the herbal coffee infusion. The total phenolic content (61.5 ± 5.1 mg GAE/g), total flavonoid content (19.3 ± 0.9 mg QE/g), and total condensed tannin (7.6 ± 0.7 mg CE/g) of herbal coffee infusion were observed to be highest of the two remaining samples. The herbal coffee extracts were used to determine all samples' antioxidant, anti-diabetic, and anti-Alzheimer activities. Using LC-MS/MS, we semi-quantified 19 phenolic metabolites. The results show numerous bioactive components in herbal coffee infusion with more potent antioxidant, antidiabetic, and anti-Alzheimer potential. Moreover, more studies must be conducted to confirm how the metabolomic profile of herbal coffee affects its flavor profile.

Tuberculosis (TB) remains a global health threat, necessitating innovative strategies for control and prevention. This comprehensive review explores the Mycobacterium tuberculosis Lysine Exporter (LysE) gene, unveiling its multifaceted roles and potential uses in controlling and preventing tuberculosis (TB). As a pivotal player in eliminating excess L-lysine and L-arginine, LysE contributes to the survival and virulence of M. tuberculosis. This review synthesizes findings from different electronic databases and includes 13 studies focused on the LysE of M. tuberculosis. The research unveils that LysE can be a potential drug target, a diagnostic marker for TB, and a promising candidate for vaccine development. The absence of LysE in the widely used BCG vaccine underscores its uniqueness and positions it as a novel area for TB prevention. In conclusion, this review underscores the significance of LysE in TB pathogenesis and its potential as a drug target, diagnostic marker, and vaccine candidate. The multifaceted nature of LysE positions it at the forefront of innovative approaches to combat TB, calling for sustained research efforts to harness its full potential in the global fight against this infectious disease.

Cranberries are rich in bioactive constituents reported to influence a variety of health benefits, ranging from improved immune function and decreased infections to reduced cardiovascular disease and more recently cancer inhibition. A review of cranberry research targeting cancer revealed positive effects of cranberries or cranberry derived constituents against 17 different cancers utilizing a variety of in vitro techniques; whereas, in vivo studies supported the inhibitory action of cranberries toward cancers of the esophagus, stomach, colon, bladder, prostate, glioblastoma and lymphoma. Mechanisms of cranberry-linked cancer inhibition include cellular death induction via apoptosis, necrosis and autophagy; reduction of cellular proliferation; alterations in reactive oxygen species; and modification of cytokine and signal transduction pathways. Given the emerging positive preclinical effects of cranberries, future clinical directions targeting cancer or premalignancy will be considered

Wilms tumor (WT), the most prevalent type of renal cancer in children, exhibits overall survival rates exceeding 90%. However, chemotherapy resistance, which occurs in approximately 10% of WT cases, is a major challenge for the treatment of WT, particularly for advanced-stage patients. In this study, we aimed to discover potential mutation markers and drug targets associated with chemotherapy resistance in advanced stage WT. We performed exome sequencing to detect somatic mutations and molecular targets in 43 WT samples, comprising 26 advanced stage WTs, of which 7 cases are chemotherapy-resistant. Our analysis revealed four genes (ALPK2, C16orf96, PRKDC, and SVIL) that correlated with chemotherapy resistance and reduced disease-free survival in ad-vanced-stage WT. Additionally, we identified driver mutations in 55 genes within the chemo-therapy-resistant group, including 14 druggable cancer driver genes. Based on the mutation profile of the resistant WT samples, we propose potential therapeutic strategies involving platinum-based agents, PARP inhibitors, and antibiotic/antineoplastic agents. Our findings provide insights into the genetic landscape of WT and offer potential avenues for targeted treatment, particularly for patients with chemotherapy resistance.

ST-segment elevation myocardial infarction (STEMI), a major cause of mortality worldwide, has been shown through epidemiological studies to have a relationship with short-term exposure to air pollutants; however, the association between air pollutants and the outcome of STEMI has not been well studied. The aim of this study was to estimate the impact of air pollutants on the outcomes of STEMI. Data on particulate matter <2.5 μm (PM2.5), <10 μm (PM10), nitrogen dioxide (NO2), and ozone (O3) at each of the 11 air monitoring stations in Kaohsiung City were collected between January 1, 2012, and December 31, 2017. Medical records of non-trauma patients aged > 20 years who had visited the ED with a principal diagnosis of STEMI were extracted. The primary outcome measure was in-hospital mortality. After adjusting for potential confounders and meteorological variables, we found that an increase in the interquartile range (IQR) in NO2 was associated with an elevated risk of in-hospital mortality in patients with STEMI. Moreover, during the warm season, an IQR increase in NO2 corresponded to a higher risk of in-hospital mortality in patients with STEMI on lag 3 (OR=3.266; 95% CI:1.203–8.864, p=0.02). Conversely, an IQR increase in PM10 was associated with an increased risk of in-hospital mortality in patients with STEMI on lag 3 (OR=2.792; 95%CI:1.115–6.993, p=0.028) during the cold season. Our study suggests that exposure to NO2 (during warm season) and PM10 (during cold season) may contribute to a higher risk of poor prognosis in patients with STEMI.

We recently reported that in the spinal cord of PPMS or SPMS patients, large areas of periplaque demyelinating lesions extend distance away from plaque borders. Such lesions are characterized by a progliotic TGF-beta 1 signature accompanied by: i) a low-grade inflammatory reaction, ii) an extensive astrocytosis and iii) a process of incomplete demyelination. It was proposed that, while efficiently dampening inflammation in MS spinal cords, TGF-beta 1 could promote astrocytosis, prevent remyelination and possibly trigger alterations of myelin synthesis. In light of these findings, a re-interpretation of two large neuropathological studies performed on MS brains and spinal cords is provided here. While results from these studies clearly showed that active plaques do not display any region-specific distribution, an important point was apparently overlooked and not discussed by the authors: a significantly higher percentage of inactive plaques was found in MS spinal cords as compared to brains and, conversely, the percentage of slowly-expanding (or smoldering) lesions was significantly lower in the spinal cord as compared to the brain. These data indicate that the spinal cord environment may be more favorable to the resolution of inflammation. Downstream of the autoimmune process leading to plaque formation, region-specific mechanisms may thus drive the outcome of active plaques. While inflammation triggers tissue destruction, inflammation may also be needed for effective tissue repair and an inappropriate dampening of inflammatory events may possibly translate into a poor level of remyelination in MS spinal cords. It is proposed here that TGF-beta 1 is involved in such a brain-spinal cord dissociation of active plaques outcome.

This study analyzes how Perceived Credibility of a 360-degree feedback and Evaluation of Outcome impact on ratees’ attitudes towards behavioral change. The study adopts a qualitative-quantitative mixed method approach. Reasoned Action Theory was selected as the theoretical framework, and ten 360-degree assessment ratees were interviewed on their perceived credibility, evaluation of outcome and attitude toward behavioral change in the 360-degree assessment practices. The qualitative inputs were analyzed under the methodology of grounded theory. Additional 159 respondents participated in the quantitative research phase of the research to validate the findings in the qualitative research phase. It was validated that Perceived Credibility, Evaluation of Outcome has impact on Attitude Toward Behavioral Change in 360-degree assessment.

Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein. Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

Extracts of Cordyceps militaris which possess the bioactive capacity such as antimicrobial activity and DPPH-free radical scavenging capacity, are applied to the serum product. This finished serum product has been evaluated the in vitro bioactivity and the stability with expect to find out a good extract with a suitable percentage used for serum product as natural materials on preservatives and antioxidation.

Cercospora beticola Sacc. is an ascomycete pathogen that causes Cercospora leaf spot in sugar beets (Beta vulgaris L.) and other related crops. The disease symptoms are characterized by circular lesions with an ash-gray centre and dark brown to purple margins on the leaves. It can lead to significant yield losses if not effectively managed. This study aims to characterize and assess the impact of bacterial biological control agents against C. beticola. Following a dual-culture screening, 18 bacteria exhibiting over 50% inhibition were selected, with six of them demonstrating more than 80% control. Identification of the bacteria was carried out through sequencing of the16S rDNA, revealing potentially 12 species belonging to six genera including Bacillus which was represented by four species. Additionally, the bacteria underwent in-depth characterization of biochemical and molecular properties, as well as plant-growth promotion. PCR detection of genes responsible for producing antifungal metabolites revealed that 83%, 78%, 89%, and 56% of the selected bacteria possessed the bacillomycin, iturin, fengycin, and surfactin encoding genes, respectively. Infrared spectroscopy analysis confirmed the presence of lipopeptide structure in the bacteria supernatant filtrate. Subsequently, the bacteria were assessed for their effect on sugar beet plants in controlled conditions. The bacteria exhibited notable capabilities, promoting growth in both roots and shoots, resulting in significant increases in root length, weight, and shoot length. The field experiment with four bacterial candidates demonstrated good performance against C. beticola compared to difenoconazole fungicide. These bacteria played a significant role in disease control, achieving a maximum efficacy of 77.42%, slightly below the 88.51% efficacy attained by difenoconazole. Additional field trials are necessary to verify the protective and growth-promoting effects of these candidates, whether applied individually, combined in consortia, or integrated with chemical inputs in sugar beet crop production.

Introduction – Gender influences the presentation and progression of various diseases. Studies regarding the impact of gender on the course and outcome of HIV demonstrate conflicting data. Studies may be biased due to socioeconomic status differences between females and males and uneven gender representation, among other factors. In order to minimize the effect of non-biological elements this study cohort compares HIV males and females with similar ethnicity and social class in 2 Israeli AIDS centers. Methods –the study is a retrospective study. The cohort consists 334 females and 223 males diagnosed with HIV during the years 2000-2015. All patients were immigrants from Ethiopia who acquired HIV heterosexually and had a similar socioeconomic status. Data regarding demographics, clinical status, virological (viral load; VL), immunological (CD4) and treatment modalities were collected for each patient. Results - At the time of HIV diagnosis, males were older (43.2 ±13.2 vs. 35.4±11.95 years; p

Aim To explore the impact of cardiovascular risk factors on the type and outcome of hypertensive crises. Additionally, to investigate the occurrence of new cardiovascular events in a six-month period for both types of hypertensive crises and to define possible risk factors that may influence this.Method The data from the hospital electronic medical records of patients who presented with hypertensive crises at the Emergency Medicine Clinic of the Clinical Center of the University of Sarajevo over a six-month period were retrospectively collected. Pregnant women were excluded. Patients who died before completing the diagnostic examination as well as patients with incomplete data were also excluded. Data collection encompassed blood pressure levels, age, sex, history of chronic hypertension, smoking status, and presence of diabetes mellitus as cardiovascular risk factors. Outcomes after initial admission and after 6 months follow up were recorded. Results The study included 243 patients: 66 (27.2%) with hypertensive emergencies and 177 (72.8%) with hypertensive urgencies. There was no significant difference between these groups in age, history of chronic hypertension, presence of dyslipidemia, smoking status, and presence of diabetes mellitus (p>0.05). Men predominated in HE, while women predominated in HU group (p<0.05). Diastolic blood pressure values were higher in HE patients (p<0.05). 98.3% of HU patients were discharged, while 92.4% of HE patients were hospitalized. Mortality after initial admission was 3%, all of whom were hypertensive emergencies. After a 6-month follow-up, there was no significant difference in the number of readmissions between these two groups (p>0.05), but mortality was significantly higher in hypertensive emergencies (15.15% vs 6.21%) (p<0.05). There was no significant difference in the investigated risk factors between patients without readmissions, with readmissions without fatal outcomes, and deceased patients (p>0.05) except for age, which was significantly higher in patients with fatal outcomes (p<0.05).Conclusion Male sex and higher diastolic blood pressure (DBP) are identified as risk factors for hypertensive emergency (HE), suggesting a higher likelihood of hospital treatment and increased intrahospital mortality. Patients with HE also exhibit a higher risk of a lethal outcome within six months. Advanced age is associated with an increased risk of six-month readmission and a lethal outcome.

Background: Optimal hypofractionated schedule of post-prostatectomy radiotherapy remains to be established. We evaluated treatment outcomes and toxicity of the moderately hypofractionated post-prostatectomy radiotherapy in 16 daily fractions delivered with IMRT/VMAT. The treatment schedule selection was motivated by limited technology resources. Methods: One hundred consecutive M0 patients with post-prostatectomy radiotherapy were evaluated. Radiotherapy indication was adjuvant (ART) in 19%, early salvage (eSRT) in 46% and salvage (SRT) in 35%. The dose prescription for prostate bed PTV was 52.8 Gy in 16 fractions of 3.3 Gy. The Common Terminology Criteria v.4 for Adverse Events scale was used for toxicity grading. Results: The median follow-up was 61 months. Five-year biochemical recurrence-free survival (bRFS) was 78.6%, distant metastases-free survival was 95.7% and overall survival was 98.8%. Treatment indication was the only significant factor for 5-year bRFS in multivariate analysis which was 84.6% vs. 67.6% for ART or eSRT vs. SRT respectively (HR 0.15, 95% CI 0.05–0.47, p=0.001). Acute GI toxicity grade 2 was recorded in 24%, grade 3 in 2% and acute GU toxicity grade 2 in 10% and no grade 3. Cumulative rate of late GI toxicity grade ≥2 was observed in 9% and late GU toxicity grade ≥2 in 16%. Conclusion: Observed results confirmed efficacy and acceptable toxicity of post-prostatectomy hypofractionated radiotherapy in 16 daily fractions.

The triple-negative breast cancer (TNBC) subtype is one of the most aggressive forms of breast cancer that has poor clinical outcome and still remains as an unmet clinical challenge. Accumulating evidence suggests that intratumoral heterogeneity or the presence of phenotypically heterogeneous cell populations within a tumor plays a crucial role in chemoresistance, tumor progression and metastasis. Increased understanding of the molecular regulators of intratumoral heterogeneity will enable the development of effective therapeutic strategies in TNBC. We have identified a molecular mediator involved in intratumoral heterogeneity in breast cancer using an unbiased approach. We isolated two heterogeneous tumor cell populations from the 4T1 TNBC tumor model and phenotypic characterization revealed that the cells are distinct in terms of their morphology, proliferation and self-renewal ability in vitro; as well as primary tumor formation and metastatic potential in vivo. Further, RNA sequencing on both cell populations was performed to identify the molecular mediators underlying this heterogeneity. Bioinformatic analysis performed on the differentially expressed genes along with the Kaplan-Meier survival analysis in TNBC patients identified Metastasis associated colon cancer 1 (Macc1) as the top candidate gene mediating the aggressive phenotype. The role of Macc1 in regulating the proliferative phenotype was validated using siRNA mediated gene knockdown. The role of Macc1 in the aggressive cancer cell phenotypes and disease progression is being studied further using a small molecule transcriptional inhibitor of Macc1 in cell line and animal models, thus increasing our understanding of the molecular underpinnings of intratumoral heterogeneity in breast cancer that is critical to the improvement in the treatment of women currently living with the highly aggressive TNBC subtype.

Increasing global concern over COVID-19 has recently brought greater attention to studies due to the ease of person-to-person transmission and the current lack of effective antiviral therapy. Here, we proposed the application of the adverse outcome pathway (AOP) framework to support re-search on the pathogenesis of viral disease. We first constructed adverse outcome pathways (AOPs) applicable to COVID-19 management to understand whether the infection causes severe acute respiratory distress. Based on the AOP framework where mechanistic elucidation of the pathway from the interaction of chemicals (or viruses) to apical endpoints is represented, our COVID-19 AOP indicated that the molecular initiating event (MIE) was angiotensin-converting enzyme 2 (ACE2) interaction, and the key events (KEs) were the increased pro-inflammatory cytokines in immune cells, with increased mortality as an apical adverse outcome (AO). However, there is still limited information on the toxicity mechanisms of AOPs in COVID-19; therefore, detailed KEs and AOs on toxicity mechanisms will be required to fill these gaps in the data. This study demonstrated that the COVID-19 AOP framework is a suitable tool to design new drugs and to integrate crowded-sourced information for the battle against the COVID-19 pandemic.

: Microplastics and nanoplastics (MNPs) are becoming an increasingly severe global problem due to their widespread distribution and complex impact on living organisms. Apart from their environmental impact, the effects of MNPs on living organisms have also continued to attract attention. The harmful impact of MNPs has been extensively documented in marine invertebrates and larger marine vertebrates like fish. However, the research on the toxicity of these particles on mammals is still limited, and their possible effects on humans are poorly understood. Considering that MNPs are commonly found in food or food packaging, humans are primarily exposed to them through ingestion. It would be valuable to investigate the potential harmful effects of these particles on gut health. This review focuses on recent research exploring the toxicological impacts of micro- and nanoplastics on the gut, as observed in human cell lines and mammalian models. Available data from various studies indicate that the accumulation of MNPs in mammalian models and human cells may result in adverse consequences, in terms of epithelial toxicity, immune toxicity, and disruption of gut microbiota. The paper also discusses the current research limitations and prospects in this field, aiming to provide a scientific basis and reference for further studies on the toxic mechanisms of micro- and nanoplastics.

This study aimed to translate and psychometrically validate the Neck Outcome Score (NOOS) in the Polish population according to the recommendations of American Academy of Orthopedic Surgeons (AAOS) for the Cross-Cultural Adaptation of Health Status Measures. Participants completed the NOOS, Neck Disability Index (NDI), and Visual Analogue Scale (VAS) for pain assessment. The questionnaires were completed by 57 women and 32 men with cervical spine ailments. A retest was performed in all patients after 48 hours. The analysis confirmed the high internal consistency (Cronbach's alpha of 0.95) of the Polish NOOS. No floor / ceiling effects were observed. The Polish NOOS showed a significant correlation with NDI (0.87; p<0.001) and VAS (0.79; p<0.001). The intraclass correlation coefficient (ICC) for the test-retest was found to be high (0.97). The Polish version of NOOS can be used for clinical and research purposes as an equivalent to the original English version. This study contributes to the area of patient-reported outcome measures available in the Polish language.

Background and Objectives: Jehovah's Witnesses (JW) reject the transfusion of blood components based on their religious beliefs even if they are in danger of harm or death. In cardiac surgery, this significantly reduces the margin of safety and leads to ethical conflicts. Informed consent should be carefully documented and the patient's family should be involved. This study aims to compare the postoperative course of JW who underwent major cardiac surgery with a similar population of non-Witnesses (NW). Patients and Methods: Demographic, procedural, and postoperative data of all consecutive JW who underwent cardiac surgery at our institution were obtained from the records. They were compared with a propensity score matched group of NW. Anemic JW were treated with erythropoietin and/or iron as needed. Cardiac surgery was performed by experienced surgeons using median sternotomy and cardiopulmonary bypass. Common blood-sparing techniques were routinely used. Periprocedural morbidity and mortality were statistically evaluated for both groups. Results: 32 JW and 64 NW were part of the matched dataset showing no demographic or procedural differences. EPO was used preoperatively in 34.4% and postoperatively in 15.6% of JW but not in NW. Preoperative hemoglobin levels were similar (JW, 8.09±0.99 mmol/l; NW, 8.18±1.06; p=0.683). JW did not receive any transfusions except for one who revoked, while NW transfusion rates were 2.5±3.1 units for red cells (p&lt;0.001) and 0.3±0.8 for platelets (p=0.018). Postoperative levels differed significantly for hemoglobin (JW, 6.05±1.00 mmol/l; NW, 6.88±0.87; p&lt;0.001), and hematocrit (JW, 0.29±0.04; NW, 0.33±0.04; p&lt;0.001) but not for creatinine. Early mortality was similar (JW, 6.3%; NW, 4.7%; p=0.745). There were more pacemakers and pneumonias in JW, while all other postoperative conditions were not different. Conclusions: Real-world data indicate that Jehovah's Witnesses can safely undergo cardiac surgery provided that patients are preconditioned and treated by experienced surgeons who use blood-saving strategies. Postoperative anemia is observed but does not translate into a worse clinical outcome. This is consistent with other studies.

Background: Idiopathic normal pressure hydrocephalus is a syndrome with neuroradiological findings and clinical pattern characteristic but not specific for the pathology. Since the prevalence is growing due to the rapidly aging society, standardized and validated protocol for diagnosis is needed, also because this condition may mimic other disorders among elderly such as Parkinson's and Alzheimer's disease. Material and methods: We analysed data from 44 patients with suspect diagnosis of idiopathic normal pressure hydrocephalus with age > 60 years, clinical triad and neuroradiological pattern examined in our ward from November 2018 to November 2022. Neu-ropsychological assessment includes Mini Mental State Examination and Mental Deterioration Battery. Motor scores were collected from gait and balance tests. The evaluation was performed before and after an extended lumbar drainage last 48h. Patients who has scores improvement after the extended lumbar drainage, undergo ventriculoperitoneal shunt with a programmable valve. Results: All patients undergo neuropsychological assessment and motor tests, only 2 patients were unable to perform motor tests because bedridden. 16 patients showed no benefit from the tests, in 2 cases even a worsening of cognitive performance. 28 patients showed an improvement in their performances, but in most cases the improvement involved only the neuropsychological as-sessment. All patients underwent ventriculoperitoneal shunt have had a typical answers pattern in Mental Deterioration Battery test. We performed 9 ventriculoperitoneal shunt and 1 ventricu-lo-atrial shunt. Conclusions: Qualitative neurocognitive tests come out to be more sensitive compared to quantitative neurocognitive tests in identifying patients with suspected idiopathic normal pressure hydrocephalus benefiting from extended lumbar drainage test and then un-derwent surgical treatment. This could be considered a valid screening in elderly patients with suspected idiopathic normal pressure hydrocephalus in order to minimize the number of invasive procedures. More studies are necessary to validate this tool.

This paper presents an Application Based Active Learning (ABAL) methodology on Power Electronics (PE) and Electric Machines (EM) as a hybrid laboratory course for the undergraduate students to design and implement the real-world engineering problems. The ABAL is a type of active learning which is a branch of Learner-centered teaching (LCT). The DC/DC converter along with the speed control of DC separately excites the motor. In addition, a DC/AC converter is designed to control the speed of an induction motor. The results are then investigated on a hardware platform under the ABAL experimental methodology. This paper also discusses the problem identification selection of the equipment, circuit design, hardware mounting and critical analysis of the results acquired from the hybrid laboratory. The ABAL methodology was evaluated based on student satisfaction, feedback, grades and interest to solve the real-world problem rather than cramming the engineering concepts and fulfill so-called lab routine and tasks

Statistical mechanics investigates how emergent properties of macroscopic systems (such as temperature and pressure) relate to microscopic state fluctuations. The underlying idea is that global statistical descriptors of order and variability can monitor the relevant dynamics of the whole system at hand. Here we test the possibility of extending such an approach to psychotherapy research investigating the possibility of predicting the outcome of psychotherapy on the sole basis of coarse-grained empirical macro-parameters. Four good-outcome and four poor-outcome brief psychotherapies were recorded, and their transcripts coded in terms of standard psychological categories (abstract, positive emotional and negative emotional language pertaining to patient and therapist). Each patient-therapist interaction is considered as a discrete multivariate time series made of subsequent word-blocks of 150-word length, defined in terms of the above categories. Static analysis (Principal Component Analysis) highlighted a substantial difference between good-outcome and poor-outcome cases in terms of mutual correlations among those descriptors. In the former, the patient’s use of abstract language correlated with therapist’s emotional negative language, while in the latter it co-varied with therapist’s emotional positive language, thus showing the different judgment of the therapists regarding the same variable (abstract language) in poor and good outcome cases. On the other hand, the dynamic analysis, based on five coarse-grained descriptors related to variability, degree of order and complexity of the series, demonstrated a relevant case-specific effect, pointing to the possibility of deriving a consistent picture of any single psychotherapeutic process. Overall, the results showed that the systemic approach to psychotherapy (an old tenet of psychology) is mature to shift from a metaphorical to a fully quantitative status.

The influenza virus has been the primary cause of the pandemic, posing a constant threat to human society. Due to its genetic evolution and continuous outbreak, antiviral research currently focuses on exploring a novel lead agent. A comprehensive antiviral screening discovered a marine bacterium whose extract exerted excellent efficacy against influenza viruses. Parerythrobacter sp. M20A3S10, a novel strain under the family Erythrobacteraceae, could produce carotenoids exhibiting antiviral and anticancer activity by enhancing the cellular immune system. Post-treatment of M20A3S10 extract showed outstanding therapeutic indexes: against influenza virus A/PR8 (H1N1) [selectivity index (SI) = 24.0], A/Wisconsin/15/2009 (H3N2) (SI = 30.1) and B/Florida/78/2015 (SI = 38.2). Comparably, the effectiveness was demonstrated against Zika virus (ZIKV) and dengue virus type 2 (DENV2) with an SI of 22.5 and 24.1, respectively, namely broad-spectrum activity. Of note, the antiviral responses resulted from the common replication mechanism between IAV, ZIKV, and DENV2. The stimulation of apoptosis-mediated cellular immunity prevented the viral release and protected the host, suggesting that switching from necroptosis to apoptosis is a novel antiviral target. Although the specific compound affecting the antiviral activity was not identified, its promising efficacy with broad activity will contribute to developing a strategy for preventing future pandemics.

Hypertensive diseases of pregnancy (HDP) represent a global clinical challenge, affecting 5-10% of women and leading to complications for both maternal well-being and fetal development. At the heart of these complications is endothelial dysfunction, with oxidative stress emerging as a pivotal causative factor. The reduction in nitric oxide (NO) bioavailability is a vital indicator of this dysfunction, culminating in blood pressure dysregulation. In the therapeutic context, although antihypertensive medications are commonly used, they come with inherent concerns related to maternal-fetal safety, and a percentage of women do not respond to these therapies. Therefore, alternative strategies that directly address the pathophysiology of HDP are required. This article focuses on the potential of the nitrate-nitrite-NO pathway, abundantly present in dark leafy greens and beetroot, as an alternative approach to treating HDP. The objective of this review is to discuss the prospective antioxidant role of nitrate. We hope our discussion paves the way for using nitrate to improve endothelial dysfunction and control oxidative stress, offering a potential therapy for managing HDP.

Background Obesity compromises the health of a woman's pregnancy and her newborn. Aim: To describe weight-gaining changes throughout pregnancy and evaluating outcomes for the mother and the baby. Methods A retrospective review of women who delivered singletons using Large Perinatal Registry. According to their BMI, patients were categorized into four categories: underweight, normal, overweight, and obese. Mode of delivery, gestational diabetes, hypertensive diseases, obstetric cholestasis, and postpartum hemorrhage were the main maternal outcome measures. The newborn outcome indicators were birth weight, NICU hospitalization, premature birth, and stillbirth. Results The study sample included 2,352 natives (25%) and 7,058 expatriates (75%). The majority of the sample (4726) were aged 20-29 years, 43.6% were aged 30-39 years, and 2.1% and 3.9% were aged 19 years and 40 years respectively. The incidence of hypertension, obstetric cholestasis, diabetes, postpartum hemorrhage, and cesarean section varied among the entire sample. In the underweight group, the incidence of CS was 15.7%, in the normal weight group (24.9%), in the overweight group (31.3%), and in the obese group (41%). Hypertensive disorders were 3 times more prevalent in obese women than in normal-weight women (2%), and 5.3% of obese women had PPH compared to 5. 6% of women of normal weight. The underweight groups gained the most weight during pregnancy, whereas the obese gained the least. Conclusions A significant proportion of pregnant women in our sample will become obese by the time of delivery. Obesity during pregnancy is associated with negative maternal and fetal outcomes.

BACKGROUND: Acute stroke is a time-critical emergency where diagnosis and acute management are highly dependent upon accuracy of patient’s history. We hypothesised that language barrier is associated with delayed onset time to thrombolysis and poor clinical outcomes. AIM: To evaluate the effect of language barriers on time to thrombolysis and clinical outcomes in acute ischemic stroke. METHODS: This is a retrospective study of all patients admitted to a metropolitan stroke unit (Melbourne, Victoria, Australia) with an acute ischemic stroke treated with tissue plasminogen activator between 1/2013 and 9/2017. Baseline characteristics, thrombolysis time intervals, length of stay, discharge destination, and in-hospital mortality were compared between patients with and without a language barrier using multivariate analysis after adjustment for age, sex, stroke severity, premorbid modified Rankin Scale (mRS) and Charlson Comorbidity Index (CCI). Language barriers were defined as a primary language other than English. RESULTS: A total of 374 patients were included. Of this, 76 patients (20.3%) had a language barrier. Mean age was 5 years older for patients with language barriers (76.7 vs 71.8 years, P=0.004). Less non-English speaking patients had pre-morbid mRS score of zero (P=0.002) and more had pre-morbid mRS score of one or two (P=0.04). There was no statistically significant difference between two groups in terms of stroke severity on presentation (P=0.06). The onset to needle time was significantly longer in patients with a language barrier (188 min vs 173 min, P=0.04). Onset to arrival and door to imaging times were surprisingly similar between the two groups. However, imaging to needle time was 9 minutes delayed in non-English speaking patients with a marginal P value (65 vs 56 min, P=0.06). patients with language barriers stayed longer in stroke unit stay (6 vs 4 days, P=0.02) and had higher rates of discharge to residential aged care facilities in those admitted from home (9.2% vs 2.3%, P=0.02). In-hospital mortality was not different between two groups (P=0.8) CONCLUSION: In this study language barriers were associated with almost 14 min delay in thrombolysis. The delay was mostly attributable to imaging to needle time. Language barriers were also associated with poorer clinical outcomes.

Worldwide, approximately 15 million people per year suffer from stroke. With about 5 million deaths, stroke is the second most common cause of death and a major cause of long-term disability. It is estimated that about 25% of people older than 85 years will develop stroke. Cannabis sativa and derived cannabinoids are used for recreational and medical purposes for many centuries. However, due to past legal status, research faced restrictions and cannabis use was stigmatized for potential negative impacts on health. With the legalization of cannabis in many countries of the world, cannabis and cannabis-derived substances such as cannabinoids and terpenes have gained more interest in medical research. Several medical effects of cannabis have been scientifically proven and potential risks were identified. In the context of stroke, the role of cannabis is controversial. Negative impact of cannabis use on stroke has been reported through anecdotal case reports and some population-based studies. However, potential beneficial effects of specific cannabinoids are described in animal studies under certain conditions. In this review, the existing body of evidence regarding the negative and positive impacts of cannabis use prior to stroke will be critically appraised.

Injuries to humans caused by wild animals, particularly bears, are rarely mentioned in the literature. The frequency of such injuries is high in Siberia, which is a territory surrounded by dense forests and is a habitat of brown bears. Only for the last 4 months (September - December) 4 episodes of bear attacks on humans were registered in Khakassia, Russia. We present a clinical case of rehabilitating a patient after a bear attack for multiple fragmentary fracture of the facial skeleton with displacement of bone fragments, subcutaneous emphysema of soft tissues of the face, parietal and right occipital regions, and paranasal sinus hemorrhage on the left side. The nature of the injury was enhanced by the trauma to the upper extremity, with which the patient defended himself against the animal. In addition to the damage to the face, the bear tried to open the cranium, which was evidenced by 4 furrows from the canines, 2 on the frontal and 2 on the occipital bones of the skull. The complex treatment of the patient included both maxillofacial and reconstructive surgery, and at the stage of outpatient treatment the formation of normotrophic scars with the help of neodymium laser and injections of heterogeneous composition consisting of micro-particles of "cross-linked" collagen of animal origin, placed in a gel identical to the natural extracellular matrix.

(1) Background: As Patient-reported outcome measures face challenges with low response rate on surveys, different incentive mechanism have been proposed to achieve a higher response rate. However, it seems that monetary incentives are the only mechanism with proven effect. Nevertheless, it is less likely to be used than other mechanisms due to the monetary cost. (2) Methods: In this research work, a cryptographic scheme for rewarding patients with cryptographic tokens is developed and implemented on the Ethereum test network. (3) Results: The model is able to distribute decentralised tokens to patients who complete the PROMs in a fair, private, decentralised approach. The token can be further used by patients to exchange more healthcare services, encouraging more patients to participate in PROMs. At the same time, an IER detection method is built to improve the quality of PROMs, avoiding the healthcare provider paying for meaningless PROMs from patients who barely participate for incentives. (4) Conclusions: This work provides an privacy-preserving incentive model to increase the response rate for PROMs surveys. Our model prevents patients providing invalid responses to gain rewards.

The most important predictors for outcomes after ischemic stroke, that is, for health deterioration and death, are chronological age and stroke severity; gender, genetics and lifestyle / environmental factors also play a role. Of all these, only the latter can be influenced after the event, even though recurrent stroke may be prevented by antiaggregant/anticoagulant therapy, angioplasty of high-grade stenoses, and treatment of cardiovascular risk factors. Moreover, blood cell composition and protein biomarkers such as C-reactive protein or interleukins in serum are frequently considered as biomarkers of outcome. We surveyed protein biomarkers that were reported to be predictive for outcome after ischemic stroke, specifically considering biomarkers that predict long-term outcome (≥3 months) and that are measured over the first days following the event. We classified the protein biomarkers as immune‑inflammatory, coagulation-related, and adhesion-related biomarkers. Some of these biomarkers are closely related to cellular senescence and, in particular, to the inflammatory processes that can be triggered by senescent cells. Moreover, the processes that underlie inflammation, hypercoagulation and cellular senescence connect stroke to cancer, and biomarkers of cancer-associated thromboembolism, as well as of sarcopenia, overlap strongly with the biomarkers discussed here. Finally, we demonstrate that most of the outcome-predicting protein biomarkers form a close-meshed functional interaction network, suggesting that the outcome after stroke is partially determined by an interplay of molecular processes relating to inflammation, coagulation, cell adhesion and cellular senescence.

In clinical diagnostics and longitudinal studies, the reproducibility of MRI assessments is of high importance in order to detect pathological changes, but developments in MRI hard- and software often outrun extended periods of data acquisition and analysis. This could potentially introduce artefactual changes or mask pathological alterations. However, if and how changes of MRI hardware, scanning protocols or preprocessing software affect complex neuroimaging outcomes from e.g. diffusion weighted imaging (DWI) remains largely understudied. We therefore compared DWI outcomes and artefact severity of 121 healthy participants (age range 19-54 years) who underwent two matched DWI protocols (Siemens product and Center for Magnetic Resonance Research sequence) at two sites (Siemens 3T Magnetom Verio and Skyra^fit). After different preprocessing steps, fractional anisotropy (FA) and mean diffusivity (MD) maps,obtained by tensor fitting, were processed with tract-based spatial statistics (TBSS). Inter-scanner and inter-sequence variability of skeletonised FA values reached up to 5% and differed largely in magnitude and direction across the brain. Skeletonised MD values differed up to 14% between scanners. We here demonstrate that DTI outcome measures strongly depend on imaging site and software, and that these biases vary between brain regions. These regionally inhomogeneous biases may exceed and considerably confound physiological effects such as ageing, highlighting the need to harmonise data acquisition and analysis. Future studies thus need to implement novel strategies to augment neuroimaging data reliability and replicability.

The prevalence and case fatality rates of Pediatric Lassa fever disease (LFD) are not well documented. This study was aimed at determining the prevalence, pattern and outcome of Pediatric LFD. It was a prospective observational study. A total of 183 subjects that met the criteria for LFD suspects were recruited consecutively and subjected to Lassa virus PCR test. Structured questionnaire was used to collect information. Of the 183 children recruited, 24 tested positive to Lassa virus PCR, giving a positivity rate of 13.1%. Mean duration of illness at presentation was 8.54 ± 3.83 days. Fever, abdominal pain and vomiting were the three highest presenting complaints. Seven out of 24 children died giving a case fatality rate (CFR) of 29.2%. Subjects with bleeding, poor urine output, convulsions and unconsciousness were more likely to die of LFD. Positivity and CFR of LFD are high. Improved case finding and prompt treatment is advocated.

Background. Oral anticoagulants (OACs) reduce stroke and systemic embolism (SE) in patients with atrial fibrillation (AF) but increase the risk of major bleeding (MB). No study has addressed the incidence and outcomes of bleeding in AF patients in the Middle East (ME). The Jordan AF study evaluated clinical profiles and one-year outcomes of AF patients who sustained bleeding events. Methods. Patients in 29 hospitals and clinics (May 2019 - December 2020) were enrolled and followed up for one year. Demographics and one-year events were compared in patients with or without bleeding. Results. Of 2018 patients enrolled; 166 patients sustained MB or clinically relevant non-major (CRNM) bleeding (8.2 events per 100 patient-years), including 47 patients who had MB (2.3 events per 100 patient-years). Compared with 1852 (91.8%) patients who did not have bleeding, patients with MB were older and had a higher prevalence of hypertension, diabetes mellitus (DM), heart failure, and malignancy, More patients with MB than those with no bleeding were using OACs (93.6% vs. 78.9%, p=0.02). Patients with MB had significantly higher one-year rates of stroke/SE (23.4% vs. 3.6%, p<0.0001) and all-cause mortality (31.9% vs 11.6%, p=0.001). Independent predictors of MB were stroke/SE (OR 10.8, 95% CI 5.3-21.9, p<0.0001), malignancy (3.4, 1.3-8.5, p=0.01), use of OACs (4.4, 1.3-14.7, p=0.02) and DM (1.9, 1.0-3.5, p=0.04). Conclusions. MB and CRNM bleeding occurred in (≈8%) of patients with AF at one year. Patients with MB (≈2%) had worse baseline clinical profiles and one-year prognosis compared with those who did not have bleeding. Keywords: Atrial fibrillation; Major bleeding events; Clinically-relevant non-major bleeding; Oral anticoagulants; Middle Eastern population; Prognosis. Clinical studies registration: the study is registered on clinicaltrials.gov (unique identifier number NCT03917992).

Cutaneous mycoses are common infections whose treatment has become more complex due to increasing antifungal resistance and the need for prolonged therapies, hindering patient adher-ence and increasing the incidence of adverse effects. Consequently, the use of physical therapies, especially photodynamic therapy (PDT), has increased for the treatment of onychomycosis due to its antimicrobial capacity mediated by the production of reactive oxygen species. This study investigates the in vitro effect of the combination of blue light (448 nm) and red light (645 nm) with terbinafine on the cell viability of human keratinocytes and the production of reactive ox-ygen species. The combination of terbinafine and blue light exhibits a synergistic effect on the production of reactive oxygen species and a significant increase in the expression of superoxide dismutase (SOD), an enzyme involved in the reduction of superoxide ions (O2-) and the genera-tion of hydrogen peroxide (H2O2). Such effect could be useful in clinical practice to improve the response of cutaneous mycoses to pharmacological treatment, reduce their toxicity, and shorten their duration.

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and fetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, known for maintaining immune tolerance, are crucial in pregnancy to prevent immune-mediated rejection of the fetus. In HDP, Treg numbers and function imbalance are observed, correlating with disease severity. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring fetal acceptance and placental development. In contrast, HDP is associated with Treg dysfunction, marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, where Tregs fail to adequately modulate the maternal immune response against fetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, the review acknowledges the complexity of translating these findings into effective clinical therapies, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.